Nutrient chapter

Ibuprofen

A 2-arylpropionic acid non-steroidal anti-inflammatory drug, sold and swallowed as a racemate. Unlike aspirin it inhibits cyclooxygenase reversibly and competitively rather than by acetylating it. The racemate is recorded here as an entity distinct from each of its two enantiomers, which are not linked to it or to each other as a family: only S(+)-ibuprofen inhibits cyclooxygenase-1, by 32 to 96 fold depending on the readout, while at cyclooxygenase-2 the two are indistinguishable; only R(-)-ibuprofen is activated to a coenzyme A thioester, which is what drives the one-way inversion of R to S and what gets R esterified into body triacylglycerol; and the two are cleared by different cytochromes. Context-specific entity; species, compartment and exposure are stated on each claim.

38 recorded mechanisms · 7 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

A mean of 63 plus or minus 6% of an administered dose of R(-)-ibuprofen was stereospecifically inverted to the S(+) enantiomer in four healthy male subjects, with no measurable inversion of S(+) to R(-), while the kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode, likely reflecting an interaction at plasma protein binding sites, and formation of ester glucuronide conjugates stereoselectively favoured the S enantiomer.
R(-)-ibuprofen → S(+)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
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experimental_model
Four healthy male subjects given racemic ibuprofen and each enantiomer separately
exposure
800 milligrams racemic ibuprofen and 400 milligrams of each enantiomer, on separate occasions
limitations
The design that matters: giving each enantiomer alone as well as the racemate is the only way to see the inversion and the interaction between them. Four subjects.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
Roughly two thirds of the R half turns into the S half, and none of it comes back.
primary_references
[ibu-p4005104] Stereoselective disposition of ibuprofen enantiomers in man. (1985). https://pubmed.ncbi.nlm.nih.gov/4005104/ DOI: 10.1111/j.1365-2125.1985.tb02694.x
tissue_or_cell_type
Whole body
trigger_kind
biomarker_context Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 71–82
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four healthy male subjects given racemic ibuprofen and each enantiomer separately · source_derived_draft · unverified_draft
### ibu-sixty-three-percent-inverts A mean of 63 plus or minus 6% of an administered dose of R(-)-ibuprofen was stereospecifically inverted to the S(+) enantiomer in four healthy male subjects, with no measurable inversion of S(+) to R(-), while the kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode, likely reflecting an interaction at plasma protein binding sites, and formation of ester glucuronide conjugates stereoselectively favoured the S enantiomer. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Roughly two thirds of the R half turns into the S half, and none of it comes back. organism: Human tissue_or_cell_type: Whole body experimental_model: Four healthy male subjects given racemic ibuprofen and each enantiomer separately limitations: The design that matters: giving each enantiomer alone as well as the racemate is the only way to see the inversion and the interaction between them. Four subjects. exposure: 800 milligrams racemic ibuprofen and 400 milligrams of each enantiomer, on separate occasions evidence_span: {"source_cache": "artifacts/ibuprofen-research/4005104.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "81a2d4fb66dca9706eb1bd4119a918b24385de69633f4c4d01692e7c5bd805d1", "start_char": 0, "end_char": 945, "text_sha256": "81a2d4fb66dca9706eb1bd4119a918b24385de69633f4c4d01692e7c5bd805d1"} [ibu-p4005104] Stereoselective disposition of ibuprofen enantiomers in man. (1985). https://pubmed.ncbi.nlm.nih.gov/4005104/ DOI: 10.1111/j.1365-2125.1985.tb02694.x
Complete structured claim and evidence
Chiral inversion of deuterium-labelled R-ibuprofen in the rat yields S-ibuprofen in a process involving quantitative loss of the deuterium atom originally at C-2, labelling at C-2 introduces no measurable kinetic deuterium isotope effect, and metabolism leads to the appearance of R-ibuprofen molecules labelled with four deuteriums, on which basis the proposed mechanism invokes stereoselective formation of the coenzyme A thioester of R-ibuprofen and its conversion to the corresponding enolate tautomer, affording a symmetrical intermediate through which racemization occurs in vivo.
R-ibuprofenoyl-coenzyme A thioester → The symmetrical enolate tautomer of the ibuprofenoyl-CoA thioester source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/1676645.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543", "start_char": 0, "end_char": 1438, "text_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543"}
experimental_model
Deuterium labelling with stereoselective gas chromatography and mass spectrometry in male Sprague-Dawley rats
exposure
R-ibuprofen and R-ring-2H4;2-2H ibuprofen at 7.5 milligrams per kilogram each, given orally together
limitations
The isotope design pins the chemistry: it shows which hydrogen is lost, that losing it is not rate-limiting, and that the intermediate is symmetrical. A rat study.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
The molecule loses one hydrogen, passes through a shape with no handedness at all, and can come out either way.
primary_references
[ibu-p1676645] Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat. (1991). https://pubmed.ncbi.nlm.nih.gov/1676645/ DOI: 10.1016/s0090-9556(25)07135-1
tissue_or_cell_type
Plasma and urine
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 84–95
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Deuterium labelling with stereoselective gas chromatography and mass spectrometry in male Sprague-Dawley rats · source_derived_draft · unverified_draft
### ibu-symmetrical-intermediate Chiral inversion of deuterium-labelled R-ibuprofen in the rat yields S-ibuprofen in a process involving quantitative loss of the deuterium atom originally at C-2, labelling at C-2 introduces no measurable kinetic deuterium isotope effect, and metabolism leads to the appearance of R-ibuprofen molecules labelled with four deuteriums, on which basis the proposed mechanism invokes stereoselective formation of the coenzyme A thioester of R-ibuprofen and its conversion to the corresponding enolate tautomer, affording a symmetrical intermediate through which racemization occurs in vivo. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The molecule loses one hydrogen, passes through a shape with no handedness at all, and can come out either way. organism: Rat tissue_or_cell_type: Plasma and urine experimental_model: Deuterium labelling with stereoselective gas chromatography and mass spectrometry in male Sprague-Dawley rats limitations: The isotope design pins the chemistry: it shows which hydrogen is lost, that losing it is not rate-limiting, and that the intermediate is symmetrical. A rat study. exposure: R-ibuprofen and R-ring-2H4;2-2H ibuprofen at 7.5 milligrams per kilogram each, given orally together evidence_span: {"source_cache": "artifacts/ibuprofen-research/1676645.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543", "start_char": 0, "end_char": 1438, "text_sha256": "84a6a246386fa4fee28b69fb088aa21f2bc496addf424bd1c03c64eeaf159543"} [ibu-p1676645] Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat. (1991). https://pubmed.ncbi.nlm.nih.gov/1676645/ DOI: 10.1016/s0090-9556(25)07135-1
Complete structured claim and evidence
Ibuprofen epimerization in humans is virtually irreversible from R to S, and 2-arylpropionyl-CoA epimerase readily converts R-ibuprofen-CoA into its S counterpart in active subcellular hepatic preparations, with examination of epimerase activity across tissues indicating that this metabolism occurs mainly in liver and kidney; reduced renal clearance together with metabolic bioactivation from inversion may raise plasma levels of the active species unpredictably.
2-arylpropionyl-CoA epimerase → R-ibuprofenoyl-coenzyme A thioester source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/1680979.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc", "start_char": 0, "end_char": 1119, "text_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc"}
experimental_model
Enantioselective high performance liquid chromatography in humans with active subcellular hepatic preparations from rats
exposure
Racemic and single-enantiomer ibuprofen, with R-ibuprofen-CoA applied to subcellular fractions
limitations
Establishes the epimerase step directly on the thioester. The tissue survey is in rat; the human arm is the demonstration that inversion is one-way.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human and rat
plain_language
An enzyme flips the activated form from one hand to the other, mostly in the liver and kidney.
primary_references
[ibu-p1680979] Metabolic inversion of stereoisomeric ibuprofen in man. (1991). https://pubmed.ncbi.nlm.nih.gov/1680979/
tissue_or_cell_type
Liver and kidney
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 97–108
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enantioselective high performance liquid chromatography in humans with active subcellular hepatic preparations from rats · source_derived_draft · unverified_draft
### ibu-epimerase-acts-on-the-thioester Ibuprofen epimerization in humans is virtually irreversible from R to S, and 2-arylpropionyl-CoA epimerase readily converts R-ibuprofen-CoA into its S counterpart in active subcellular hepatic preparations, with examination of epimerase activity across tissues indicating that this metabolism occurs mainly in liver and kidney; reduced renal clearance together with metabolic bioactivation from inversion may raise plasma levels of the active species unpredictably. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: An enzyme flips the activated form from one hand to the other, mostly in the liver and kidney. organism: Human and rat tissue_or_cell_type: Liver and kidney experimental_model: Enantioselective high performance liquid chromatography in humans with active subcellular hepatic preparations from rats limitations: Establishes the epimerase step directly on the thioester. The tissue survey is in rat; the human arm is the demonstration that inversion is one-way. exposure: Racemic and single-enantiomer ibuprofen, with R-ibuprofen-CoA applied to subcellular fractions evidence_span: {"source_cache": "artifacts/ibuprofen-research/1680979.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc", "start_char": 0, "end_char": 1119, "text_sha256": "4888135fd1db1817c370825ee8a1435b7654e68af33912093c725fe7041341cc"} [ibu-p1680979] Metabolic inversion of stereoisomeric ibuprofen in man. (1991). https://pubmed.ncbi.nlm.nih.gov/1680979/
Complete structured claim and evidence
Liver and kidney homogenates failed to invert R-ibuprofen directly even in the presence of all necessary cofactors, presumably from lack of enzymatic acyl-CoA synthesis, while the 2-arylpropionyl-CoA epimerase catalysed the transformation from either direction with high turnover and with greater catalytic efficiency for S-ibuprofen-CoA epimerization than for the R counterpart, so the acyl-CoA formation step assumes a pivotal role in controlling stereoselectivity and efficiency, and as the responsible synthetases differ between species the outcome varies: in guinea pigs the biotransformation proceeds in both directions with nearly equal efficiency whereas in humans it is virtually unidirectional and slow.
Long-chain acyl-CoA synthetase → Metabolic chiral inversion of a 2-arylpropionic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/1859831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f", "start_char": 0, "end_char": 2138, "text_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f"}
experimental_model
Comparative in vivo studies across mammalian species with in vitro epimerization of chemically synthesised ibuprofen-CoA thioester
exposure
Synthetic R- and S-ibuprofen-CoA thioesters applied to tissue homogenates, with and without cofactors
limitations
The decisive control is the failure: homogenates could not invert free R-ibuprofen even with all cofactors, which locates the species difference in the activation step rather than in the epimerase.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat, guinea pig and human
plain_language
The one-way traffic is set by which enantiomer gets activated, not by the enzyme that does the flipping.
primary_references
[ibu-p1859831] Metabolic stereoisomeric inversion of ibuprofen in mammals. (1991). https://pubmed.ncbi.nlm.nih.gov/1859831/ DOI: 10.1016/0167-4838(91)90164-u
tissue_or_cell_type
Liver and kidney
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 110–121
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative in vivo studies across mammalian species with in vitro epimerization of chemically synthesised ibuprofen-CoA thioester · source_derived_draft · unverified_draft
### ibu-the-synthetase-sets-direction Liver and kidney homogenates failed to invert R-ibuprofen directly even in the presence of all necessary cofactors, presumably from lack of enzymatic acyl-CoA synthesis, while the 2-arylpropionyl-CoA epimerase catalysed the transformation from either direction with high turnover and with greater catalytic efficiency for S-ibuprofen-CoA epimerization than for the R counterpart, so the acyl-CoA formation step assumes a pivotal role in controlling stereoselectivity and efficiency, and as the responsible synthetases differ between species the outcome varies: in guinea pigs the biotransformation proceeds in both directions with nearly equal efficiency whereas in humans it is virtually unidirectional and slow. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The one-way traffic is set by which enantiomer gets activated, not by the enzyme that does the flipping. organism: Rat, guinea pig and human tissue_or_cell_type: Liver and kidney experimental_model: Comparative in vivo studies across mammalian species with in vitro epimerization of chemically synthesised ibuprofen-CoA thioester limitations: The decisive control is the failure: homogenates could not invert free R-ibuprofen even with all cofactors, which locates the species difference in the activation step rather than in the epimerase. exposure: Synthetic R- and S-ibuprofen-CoA thioesters applied to tissue homogenates, with and without cofactors evidence_span: {"source_cache": "artifacts/ibuprofen-research/1859831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f", "start_char": 0, "end_char": 2138, "text_sha256": "39dd843ee06ac569e1f2a3af9af6af1639e06694a0f8dcd280065c686bd9902f"} [ibu-p1859831] Metabolic stereoisomeric inversion of ibuprofen in mammals. (1991). https://pubmed.ncbi.nlm.nih.gov/1859831/ DOI: 10.1016/0167-4838(91)90164-u
Complete structured claim and evidence
The R enantiomers of 2-arylpropionic acids such as ibuprofen exhibit species- and substrate-dependent metabolic chiral inversion in which only R enantiomers are activated to acyl-CoA thioesters by an acyl-CoA synthetase via an adenylate intermediate, and those thioesters are the substrates for the epimerase responsible for chiral inversion; three internal peptide sequences of the purified 42 kilodalton epimerase showed 50% or more homology with regions of enzymes involved in fatty acid metabolism.
Long-chain acyl-CoA synthetase → R(-)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/8615858.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5", "start_char": 0, "end_char": 1153, "text_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5"}
experimental_model
Purification of a 42 kilodalton epimerase from rat liver cytosol with polyclonal antibodies and peptide sequencing
exposure
R-enantiomers of 2-arylpropionic acids activated to acyl-CoA thioesters
limitations
States the activation asymmetry explicitly and provides the antibody used for tissue mapping. Peptide sequence homology is suggestive rather than functional evidence.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat and guinea pig
plain_language
The activating enzyme will only pick up the R hand, and that one fact explains the whole one-way chemistry.
primary_references
[ibu-p8615858] 2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization. (1995). https://pubmed.ncbi.nlm.nih.gov/8615858/ DOI: 10.1016/0006-2952(95)02054-3
tissue_or_cell_type
Liver and other tissues
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 123–134
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification of a 42 kilodalton epimerase from rat liver cytosol with polyclonal antibodies and peptide sequencing · source_derived_draft · unverified_draft
### ibu-only-r-is-activated The R enantiomers of 2-arylpropionic acids such as ibuprofen exhibit species- and substrate-dependent metabolic chiral inversion in which only R enantiomers are activated to acyl-CoA thioesters by an acyl-CoA synthetase via an adenylate intermediate, and those thioesters are the substrates for the epimerase responsible for chiral inversion; three internal peptide sequences of the purified 42 kilodalton epimerase showed 50% or more homology with regions of enzymes involved in fatty acid metabolism. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The activating enzyme will only pick up the R hand, and that one fact explains the whole one-way chemistry. organism: Rat and guinea pig tissue_or_cell_type: Liver and other tissues experimental_model: Purification of a 42 kilodalton epimerase from rat liver cytosol with polyclonal antibodies and peptide sequencing limitations: States the activation asymmetry explicitly and provides the antibody used for tissue mapping. Peptide sequence homology is suggestive rather than functional evidence. exposure: R-enantiomers of 2-arylpropionic acids activated to acyl-CoA thioesters evidence_span: {"source_cache": "artifacts/ibuprofen-research/8615858.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5", "start_char": 0, "end_char": 1153, "text_sha256": "16cf0cde21de3453912debe1cf25c6191784584aac6596a323e5b5c2944d74a5"} [ibu-p8615858] 2-Arylpropionyl-CoA epimerase: partial peptide sequences and tissue localization. (1995). https://pubmed.ncbi.nlm.nih.gov/8615858/ DOI: 10.1016/0006-2952(95)02054-3
Complete structured claim and evidence
The purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction.
2-arylpropionyl-CoA epimerase → Metabolic chiral inversion of a 2-arylpropionic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/8381432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6", "start_char": 0, "end_char": 1149, "text_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6"}
experimental_model
Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria
exposure
2-(4-isobutylphenyl)propionyl-CoA and related thioesters
limitations
Characterises the enzyme as a distinct protein and measures the equilibrium. Purified enzyme, so the equilibrium constant is a property of the epimerase and not of the intact animal.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body.
primary_references
[ibu-p8381432] Purification and characterization of novel "2-arylpropionyl-CoA epimerases" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0
tissue_or_cell_type
Liver cytosol and mitochondria
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 136–147
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria · source_derived_draft · unverified_draft
### ibu-equilibrium-favours-r The purified 2-arylpropionyl-CoA epimerases from rat liver cytosol and mitochondria are monomeric 42 kilodalton proteins distinct from methylmalonyl-CoA epimerase, show no bound cofactors and are unaffected by EDTA or metal ions except copper, and for 2-(4-isobutylphenyl)propionyl-CoA the equilibrium constant was estimated at 1.5 in favour of the R isomer, with evidence that proton exchange is mediated by a two-base mechanism and that an active-site carboxylic residue serves as a general base for proton abstraction. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Left to itself the enzyme slightly prefers the R form, which is the opposite of what happens in the body. organism: Rat tissue_or_cell_type: Liver cytosol and mitochondria experimental_model: Purification and kinetic characterisation of 2-arylpropionyl-CoA epimerase from rat liver cytosol and mitochondria limitations: Characterises the enzyme as a distinct protein and measures the equilibrium. Purified enzyme, so the equilibrium constant is a property of the epimerase and not of the intact animal. exposure: 2-(4-isobutylphenyl)propionyl-CoA and related thioesters evidence_span: {"source_cache": "artifacts/ibuprofen-research/8381432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6", "start_char": 0, "end_char": 1149, "text_sha256": "9fab6c9ed036c30f7dbfa01fd8499243d7066dfb510489f189a07ac4811c8ff6"} [ibu-p8381432] Purification and characterization of novel "2-arylpropionyl-CoA epimerases" from rat liver cytosol and mitochondria. (1993). https://pubmed.ncbi.nlm.nih.gov/8381432/ DOI: 10.1016/s0021-9258(18)53720-0
Complete structured claim and evidence
A complementary DNA clone encoding 2-arylpropionyl-CoA epimerase was isolated from rat liver, expressed in Escherichia coli and confirmed by measuring the rate of inversion of R-ibuprofenoyl-CoA, and significant amino acid sequence similarity was found with carnitine dehydratases from Caenorhabditis elegans at 41% and Escherichia coli at 27%, suggesting that this protein, characterised until then only for its role in drug transformation, has a function in lipid metabolism; the R enantiomer is described as inactive in terms of cyclooxygenase inhibition.
2-arylpropionyl-CoA epimerase → Bacterial and nematode carnitine dehydratases source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/9106621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf", "start_char": 0, "end_char": 1607, "text_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf"}
experimental_model
Molecular cloning and bacterial expression of 2-arylpropionyl-CoA epimerase from a rat liver complementary DNA library
exposure
Expressed epimerase assayed by rate of inversion of R-ibuprofenoyl-CoA
limitations
Identifies the gene and, through its homology, suggests the enzyme is not a drug-metabolising enzyme at all. Sequence homology is an inference about function, not a demonstration.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
The enzyme that activates this drug looks like an enzyme for handling fats, which is probably its real job.
primary_references
[ibu-p9106621] Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. (1997). https://pubmed.ncbi.nlm.nih.gov/9106621/ DOI: 10.1124/mol.51.4.576
tissue_or_cell_type
Liver
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 149–160
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Molecular cloning and bacterial expression of 2-arylpropionyl-CoA epimerase from a rat liver complementary DNA library · source_derived_draft · unverified_draft
### ibu-the-enzyme-is-a-lipid-enzyme A complementary DNA clone encoding 2-arylpropionyl-CoA epimerase was isolated from rat liver, expressed in Escherichia coli and confirmed by measuring the rate of inversion of R-ibuprofenoyl-CoA, and significant amino acid sequence similarity was found with carnitine dehydratases from Caenorhabditis elegans at 41% and Escherichia coli at 27%, suggesting that this protein, characterised until then only for its role in drug transformation, has a function in lipid metabolism; the R enantiomer is described as inactive in terms of cyclooxygenase inhibition. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The enzyme that activates this drug looks like an enzyme for handling fats, which is probably its real job. organism: Rat tissue_or_cell_type: Liver experimental_model: Molecular cloning and bacterial expression of 2-arylpropionyl-CoA epimerase from a rat liver complementary DNA library limitations: Identifies the gene and, through its homology, suggests the enzyme is not a drug-metabolising enzyme at all. Sequence homology is an inference about function, not a demonstration. exposure: Expressed epimerase assayed by rate of inversion of R-ibuprofenoyl-CoA evidence_span: {"source_cache": "artifacts/ibuprofen-research/9106621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf", "start_char": 0, "end_char": 1607, "text_sha256": "d2ece633650b8d636b2d0315b6d6486f618f7aae8a585c54558dffe344edf0cf"} [ibu-p9106621] Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. (1997). https://pubmed.ncbi.nlm.nih.gov/9106621/ DOI: 10.1124/mol.51.4.576
Complete structured claim and evidence
In hepatocytes isolated from rats with adjuvant-induced arthritis the chiral inversion rate constant of R- to S-ibuprofen and the metabolic rate constants of both enantiomers were significantly decreased to about 64 to 80% of control values, while adding serum from each group abolished the difference; adjuvant-induced arthritis decreased messenger RNA levels of acyl-coenzyme A synthetase isoforms but not of 2-arylpropionyl-CoA epimerase, and chiral inversion was inhibited by triacsin C, a specific inhibitor of acyl-CoA synthetase 1.
Adjuvant-induced arthritis in the rat → Metabolic chiral inversion of a 2-arylpropionic acid source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/18988084.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a", "start_char": 0, "end_char": 1381, "text_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a"}
experimental_model
Freshly isolated hepatocytes from control rats and rats with adjuvant-induced arthritis
exposure
S- or R-ibuprofen incubated with hepatocytes, with and without serum, and with triacsin C
limitations
Tests whether the disease being treated changes the handling of the drug. Isolated hepatocytes, and the serum arm shows the effect disappears when serum is added back.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
The inflammation the drug is prescribed for slows down the step that makes the drug active.
primary_references
[ibu-p18988084] Impaired intrinsic chiral inversion activity of ibuprofen in rats with adjuvant-induced arthritis. (2008). https://pubmed.ncbi.nlm.nih.gov/18988084/ DOI: 10.1080/00498250802483768
tissue_or_cell_type
Hepatocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 162–173
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Freshly isolated hepatocytes from control rats and rats with adjuvant-induced arthritis · source_derived_draft · unverified_draft
### ibu-arthritis-slows-inversion In hepatocytes isolated from rats with adjuvant-induced arthritis the chiral inversion rate constant of R- to S-ibuprofen and the metabolic rate constants of both enantiomers were significantly decreased to about 64 to 80% of control values, while adding serum from each group abolished the difference; adjuvant-induced arthritis decreased messenger RNA levels of acyl-coenzyme A synthetase isoforms but not of 2-arylpropionyl-CoA epimerase, and chiral inversion was inhibited by triacsin C, a specific inhibitor of acyl-CoA synthetase 1. Condition category: machinery_impairment nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The inflammation the drug is prescribed for slows down the step that makes the drug active. organism: Rat tissue_or_cell_type: Hepatocytes experimental_model: Freshly isolated hepatocytes from control rats and rats with adjuvant-induced arthritis limitations: Tests whether the disease being treated changes the handling of the drug. Isolated hepatocytes, and the serum arm shows the effect disappears when serum is added back. exposure: S- or R-ibuprofen incubated with hepatocytes, with and without serum, and with triacsin C evidence_span: {"source_cache": "artifacts/ibuprofen-research/18988084.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a", "start_char": 0, "end_char": 1381, "text_sha256": "49f5377220f47f04a74dc5e1cd5408a0b175eafbf602e536e57d80a9e8eb1f3a"} [ibu-p18988084] Impaired intrinsic chiral inversion activity of ibuprofen in rats with adjuvant-induced arthritis. (2008). https://pubmed.ncbi.nlm.nih.gov/18988084/ DOI: 10.1080/00498250802483768
Complete structured claim and evidence
In rat isolated adipocytes and hepatocytes incubated with tritiated glycerol there was a high-affinity enzymatic process for synthesis of triacylglycerol containing fenoprofen which was stereospecific for the R enantiomer, with apparent Km values of 1.0 micromolar in adipocytes and 2.8 micromolar in hepatocytes, consistent with stereospecific formation of R-2-arylpropionyl-CoA thioesters at clinically relevant unbound concentrations; a second low-affinity process in hepatocytes occurred at concentrations far above those found in man at usual doses.
R-ibuprofenoyl-coenzyme A thioester → Triacylglycerol carrying a 2-arylpropionic acid in place of a fatty acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/3377800.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "facf726355f08978d9f447e3cfbd803611011abed9f95b46970540d246ea11e6", "start_char": 0, "end_char": 962, "text_sha256": "facf726355f08978d9f447e3cfbd803611011abed9f95b46970540d246ea11e6"}
experimental_model
Rat isolated adipocytes and hepatocytes incubated with tritiated glycerol and single enantiomers of fenoprofen
exposure
R or S fenoprofen at concentrations spanning the clinically relevant unbound range
limitations
Tested with fenoprofen rather than ibuprofen, which is recorded on the claim. It shows where the activated R thioester can end up when it is not epimerised.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
The activated R form can be built into body fat as a fake fatty acid, at concentrations people actually reach.
primary_references
[ibu-p3377800] The stereospecific incorporation of fenoprofen into rat hepatocyte and adipocyte triacylglycerols. (1988). https://pubmed.ncbi.nlm.nih.gov/3377800/ DOI: 10.1016/0006-2952(88)90537-0
tissue_or_cell_type
Adipocytes and hepatocytes
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 175–186
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat isolated adipocytes and hepatocytes incubated with tritiated glycerol and single enantiomers of fenoprofen · source_derived_draft · unverified_draft
### ibu-r-enantiomer-enters-body-fat In rat isolated adipocytes and hepatocytes incubated with tritiated glycerol there was a high-affinity enzymatic process for synthesis of triacylglycerol containing fenoprofen which was stereospecific for the R enantiomer, with apparent Km values of 1.0 micromolar in adipocytes and 2.8 micromolar in hepatocytes, consistent with stereospecific formation of R-2-arylpropionyl-CoA thioesters at clinically relevant unbound concentrations; a second low-affinity process in hepatocytes occurred at concentrations far above those found in man at usual doses. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The activated R form can be built into body fat as a fake fatty acid, at concentrations people actually reach. organism: Rat tissue_or_cell_type: Adipocytes and hepatocytes experimental_model: Rat isolated adipocytes and hepatocytes incubated with tritiated glycerol and single enantiomers of fenoprofen limitations: Tested with fenoprofen rather than ibuprofen, which is recorded on the claim. It shows where the activated R thioester can end up when it is not epimerised. exposure: R or S fenoprofen at concentrations spanning the clinically relevant unbound range evidence_span: {"source_cache": "artifacts/ibuprofen-research/3377800.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "facf726355f08978d9f447e3cfbd803611011abed9f95b46970540d246ea11e6", "start_char": 0, "end_char": 962, "text_sha256": "facf726355f08978d9f447e3cfbd803611011abed9f95b46970540d246ea11e6"} [ibu-p3377800] The stereospecific incorporation of fenoprofen into rat hepatocyte and adipocyte triacylglycerols. (1988). https://pubmed.ncbi.nlm.nih.gov/3377800/ DOI: 10.1016/0006-2952(88)90537-0
Complete structured claim and evidence
After oral administration of 800 milligrams of racemic ibuprofen to six healthy male volunteers the mean time-averaged percentage unbound of the R(-) enantiomer was 0.419, significantly less than that of the S(+) enantiomer at 0.643, consistent with stereoselective plasma protein binding, and the unbound percentage of each enantiomer was concentration-dependent across the therapeutic range and influenced by the presence of its optical antipode.
R(-)-ibuprofen → S(+)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/2744069.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858", "start_char": 0, "end_char": 905, "text_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858"}
experimental_model
Equilibrium dialysis with diastereomeric derivatisation and radiochemical analysis in six healthy male volunteers
exposure
800 milligrams racemic ibuprofen orally, with each enantiomer measured in the presence of the other
limitations
Measures the two enantiomers in the presence of each other, which is the condition that actually obtains after a tablet. Six volunteers.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
Less of the R form is free in the blood than the S form, and each changes the other.
primary_references
[ibu-p2744069] Stereoselective plasma protein binding of ibuprofen enantiomers. (1989). https://pubmed.ncbi.nlm.nih.gov/2744069/ DOI: 10.1007/bf00558161
tissue_or_cell_type
Plasma
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 188–199
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Equilibrium dialysis with diastereomeric derivatisation and radiochemical analysis in six healthy male volunteers · source_derived_draft · unverified_draft
### ibu-binding-differs-between-hands After oral administration of 800 milligrams of racemic ibuprofen to six healthy male volunteers the mean time-averaged percentage unbound of the R(-) enantiomer was 0.419, significantly less than that of the S(+) enantiomer at 0.643, consistent with stereoselective plasma protein binding, and the unbound percentage of each enantiomer was concentration-dependent across the therapeutic range and influenced by the presence of its optical antipode. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Less of the R form is free in the blood than the S form, and each changes the other. organism: Human tissue_or_cell_type: Plasma experimental_model: Equilibrium dialysis with diastereomeric derivatisation and radiochemical analysis in six healthy male volunteers limitations: Measures the two enantiomers in the presence of each other, which is the condition that actually obtains after a tablet. Six volunteers. exposure: 800 milligrams racemic ibuprofen orally, with each enantiomer measured in the presence of the other evidence_span: {"source_cache": "artifacts/ibuprofen-research/2744069.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858", "start_char": 0, "end_char": 905, "text_sha256": "f73cd7aeb524ce11255efc7c629968dc35bafed4049636024dc2598c649ec858"} [ibu-p2744069] Stereoselective plasma protein binding of ibuprofen enantiomers. (1989). https://pubmed.ncbi.nlm.nih.gov/2744069/ DOI: 10.1007/bf00558161
Complete structured claim and evidence
Complementary-DNA-expressed CYP2C9 favoured formation of S-2- and S-3-hydroxyibuprofen while CYP2C8 favoured R-2-hydroxyibuprofen formation, high-affinity Km values for S-ibuprofen hydroxylation were 38 and 21 micromolar against 47 and 29 micromolar for R-ibuprofen, sulfaphenazole competitively inhibited all four hydroxylations with submicromolar Ki values, and the regio- and stereoselectivities observed in vitro were consistent with those noted in vivo.
Human cytochrome P450 2C8 → R(-)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/9296349.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb", "start_char": 0, "end_char": 2012, "text_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb"}
experimental_model
Human liver microsomes and complementary-DNA-expressed cytochromes with a bank of fourteen microsomal preparations
exposure
Both enantiomers of ibuprofen assayed for 2- and 3-hydroxylation, with sulfaphenazole, retinol and arachidonic acid as inhibitors
limitations
Assigns each enantiomer to a different cytochrome by direct comparison in the same system. In vitro microsomes, though the authors note the selectivities matched those seen in vivo.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
The body uses two different clearance enzymes for the two hands of the same molecule.
primary_references
[ibu-p9296349] Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. (1997). https://pubmed.ncbi.nlm.nih.gov/9296349/ DOI: 10.1016/s0006-2952(97)00143-3
tissue_or_cell_type
Liver microsomes
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 201–212
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human liver microsomes and complementary-DNA-expressed cytochromes with a bank of fourteen microsomal preparations · source_derived_draft · unverified_draft
### ibu-different-cytochromes Complementary-DNA-expressed CYP2C9 favoured formation of S-2- and S-3-hydroxyibuprofen while CYP2C8 favoured R-2-hydroxyibuprofen formation, high-affinity Km values for S-ibuprofen hydroxylation were 38 and 21 micromolar against 47 and 29 micromolar for R-ibuprofen, sulfaphenazole competitively inhibited all four hydroxylations with submicromolar Ki values, and the regio- and stereoselectivities observed in vitro were consistent with those noted in vivo. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The body uses two different clearance enzymes for the two hands of the same molecule. organism: Human tissue_or_cell_type: Liver microsomes experimental_model: Human liver microsomes and complementary-DNA-expressed cytochromes with a bank of fourteen microsomal preparations limitations: Assigns each enantiomer to a different cytochrome by direct comparison in the same system. In vitro microsomes, though the authors note the selectivities matched those seen in vivo. exposure: Both enantiomers of ibuprofen assayed for 2- and 3-hydroxylation, with sulfaphenazole, retinol and arachidonic acid as inhibitors evidence_span: {"source_cache": "artifacts/ibuprofen-research/9296349.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb", "start_char": 0, "end_char": 2012, "text_sha256": "19179a5f8220c1d4037113812f8968e2730ecf07c6ad94997d2661d7c6c75afb"} [ibu-p9296349] Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. (1997). https://pubmed.ncbi.nlm.nih.gov/9296349/ DOI: 10.1016/s0006-2952(97)00143-3
Complete structured claim and evidence
Population mean S-ibuprofen clearances were 3.25, 2.38 and 1.52 litres per hour in carriers of CYP2C9 genotypes *1/*1, *1/*3 and *3/*3 respectively while the *2 variant had no significant effect, and ex vivo formation of thromboxane B2 reflecting cyclooxygenase-1 inhibition depended significantly on the polymorphism, with maximal inhibition and the area under the effect-time curve larger in carriers of the slow genotypes, the same trend holding for prostaglandin E2.
The CYP2C9 isoleucine 359 leucine variant, CYP2C9*3 → S(+)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/12152005.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "314477c44dbb699b0fe3d9ab14eb7da427d88538177b4e4267ef0ad25fd407da", "start_char": 0, "end_char": 1822, "text_sha256": "314477c44dbb699b0fe3d9ab14eb7da427d88538177b4e4267ef0ad25fd407da"}
experimental_model
Population pharmacokinetic study in 21 healthy volunteers across all combinations of CYP2C9 variants
exposure
600 milligrams oral racemic ibuprofen, with thromboxane B2 and prostaglandin E2 measured ex vivo
limitations
Links a genotype to both the drug level and the enzyme effect in the same subjects. Twenty-one volunteers spread across genotype groups, so each group is small.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
People who clear the active half slowly get both more drug and more effect from the same tablet.
primary_references
[ibu-p12152005] Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. (2002). https://pubmed.ncbi.nlm.nih.gov/12152005/ DOI: 10.1067/mcp.2002.125726
tissue_or_cell_type
Plasma, platelets and monocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 214–225
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Population pharmacokinetic study in 21 healthy volunteers across all combinations of CYP2C9 variants · source_derived_draft · unverified_draft
### ibu-slow-clearance-more-effect Population mean S-ibuprofen clearances were 3.25, 2.38 and 1.52 litres per hour in carriers of CYP2C9 genotypes *1/*1, *1/*3 and *3/*3 respectively while the *2 variant had no significant effect, and ex vivo formation of thromboxane B2 reflecting cyclooxygenase-1 inhibition depended significantly on the polymorphism, with maximal inhibition and the area under the effect-time curve larger in carriers of the slow genotypes, the same trend holding for prostaglandin E2. Condition category: machinery_impairment nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: People who clear the active half slowly get both more drug and more effect from the same tablet. organism: Human tissue_or_cell_type: Plasma, platelets and monocytes experimental_model: Population pharmacokinetic study in 21 healthy volunteers across all combinations of CYP2C9 variants limitations: Links a genotype to both the drug level and the enzyme effect in the same subjects. Twenty-one volunteers spread across genotype groups, so each group is small. exposure: 600 milligrams oral racemic ibuprofen, with thromboxane B2 and prostaglandin E2 measured ex vivo evidence_span: {"source_cache": "artifacts/ibuprofen-research/12152005.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "314477c44dbb699b0fe3d9ab14eb7da427d88538177b4e4267ef0ad25fd407da", "start_char": 0, "end_char": 1822, "text_sha256": "314477c44dbb699b0fe3d9ab14eb7da427d88538177b4e4267ef0ad25fd407da"} [ibu-p12152005] Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. (2002). https://pubmed.ncbi.nlm.nih.gov/12152005/ DOI: 10.1067/mcp.2002.125726
Complete structured claim and evidence
The CYP2C8*3 allele influenced the pharmacokinetics of R-ibuprofen in a gene-dose manner, with plasma half-life after 400 milligrams of 2.0 hours in CYP2C8*1/*1, 4.2 hours in *1/*3 and 9.0 hours in *3/*3 individuals, alongside significant trends in area under the curve and clearance, and the allele frequency of 0.17 in this Spanish Caucasian population was higher than reported elsewhere and was associated with CYP2C9*2 at 2.4-fold the expected frequency.
The CYP2C8*3 variant allele → R(-)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/15606441.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9", "start_char": 0, "end_char": 1795, "text_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9"}
experimental_model
Genotype screening of 355 Spanish Caucasians with pharmacokinetics in 25 individuals grouped by CYP2C8 genotype
exposure
400 milligrams ibuprofen, with R-ibuprofen disposition followed by genotype
limitations
A clear gene-dose effect on the enantiomer that CYP2C9 does not handle. One population, and 25 individuals across the genotype groups.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
A common variant makes the R half linger more than four times as long.
primary_references
[ibu-p15606441] The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. (2005). https://pubmed.ncbi.nlm.nih.gov/15606441/ DOI: 10.1111/j.1365-2125.2004.02183.x
tissue_or_cell_type
Plasma
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 227–238
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype screening of 355 Spanish Caucasians with pharmacokinetics in 25 individuals grouped by CYP2C8 genotype · source_derived_draft · unverified_draft
### ibu-cyp2c8-and-the-r-hand The CYP2C8*3 allele influenced the pharmacokinetics of R-ibuprofen in a gene-dose manner, with plasma half-life after 400 milligrams of 2.0 hours in CYP2C8*1/*1, 4.2 hours in *1/*3 and 9.0 hours in *3/*3 individuals, alongside significant trends in area under the curve and clearance, and the allele frequency of 0.17 in this Spanish Caucasian population was higher than reported elsewhere and was associated with CYP2C9*2 at 2.4-fold the expected frequency. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: A common variant makes the R half linger more than four times as long. organism: Human tissue_or_cell_type: Plasma experimental_model: Genotype screening of 355 Spanish Caucasians with pharmacokinetics in 25 individuals grouped by CYP2C8 genotype limitations: A clear gene-dose effect on the enantiomer that CYP2C9 does not handle. One population, and 25 individuals across the genotype groups. exposure: 400 milligrams ibuprofen, with R-ibuprofen disposition followed by genotype evidence_span: {"source_cache": "artifacts/ibuprofen-research/15606441.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9", "start_char": 0, "end_char": 1795, "text_sha256": "60cffa777fc0b9881548e974376299ec7e970c2785586766150896cbf0561af9"} [ibu-p15606441] The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. (2005). https://pubmed.ncbi.nlm.nih.gov/15606441/ DOI: 10.1111/j.1365-2125.2004.02183.x
Complete structured claim and evidence
Ratios of half-maximal inhibitory concentrations for cyclooxygenase inhibition by D- and L-ibuprofen were 32 for native cyclooxygenase-1, 67 for the R120Q mutant and 7.1 for the Y355F mutant, and the decreased stereochemical specificity of the Y355F mutant suggests that Tyr355 is a determinant of the stereospecificity of the enzyme toward inhibitors of the 2-phenylpropionic acid class.
Tyrosine 355 of cyclooxygenase-1 → Stereochemical discrimination between enantiomers of a 2-phenylpropionic acid inhibitor source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells
exposure
D- and L-ibuprofen and flurbiprofen tested against the mutant panel
limitations
Identifies which residue does the stereochemical discrimination by changing it and watching the discrimination collapse. Ovine recombinant enzyme.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Sheep enzyme
plain_language
One tyrosine is what lets the enzyme tell the two hands of the drug apart; remove it and the difference mostly goes.
primary_references
[ibu-p8567676] Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. (1996). https://pubmed.ncbi.nlm.nih.gov/8567676/ DOI: 10.1074/jbc.271.4.2179
tissue_or_cell_type
Recombinant cyclooxygenase-1
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 240–251
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells · source_derived_draft · unverified_draft
### ibu-tyr355-reads-the-handedness Ratios of half-maximal inhibitory concentrations for cyclooxygenase inhibition by D- and L-ibuprofen were 32 for native cyclooxygenase-1, 67 for the R120Q mutant and 7.1 for the Y355F mutant, and the decreased stereochemical specificity of the Y355F mutant suggests that Tyr355 is a determinant of the stereospecificity of the enzyme toward inhibitors of the 2-phenylpropionic acid class. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: One tyrosine is what lets the enzyme tell the two hands of the drug apart; remove it and the difference mostly goes. organism: Sheep enzyme tissue_or_cell_type: Recombinant cyclooxygenase-1 experimental_model: Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells limitations: Identifies which residue does the stereochemical discrimination by changing it and watching the discrimination collapse. Ovine recombinant enzyme. exposure: D- and L-ibuprofen and flurbiprofen tested against the mutant panel evidence_span: {"source_cache": "artifacts/ibuprofen-research/8567676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda", "start_char": 0, "end_char": 2200, "text_sha256": "773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda"} [ibu-p8567676] Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. (1996). https://pubmed.ncbi.nlm.nih.gov/8567676/ DOI: 10.1074/jbc.271.4.2179
Complete structured claim and evidence
All mutants retained at least part of their activity except R120E which had none, Km values for arachidonic acid were 87 and 3300 micromolar for R120K and R120Q against 4 micromolar for native enzyme, and the R120Q mutant failed to undergo suicide inactivation during catalysis or time-dependent inhibition by flurbiprofen, results consistent with Arg120 binding the carboxylate group of arachidonate and indicating that interaction of the carboxylate of substrates and inhibitors with Arg120 is necessary for suicide inactivation and time-dependent inhibition respectively; Glu524 substitutions did not significantly change Km.
Arginine 120 of cyclooxygenase-1 → The free carboxylate group of a 2-arylpropionic acid inhibitor source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/8567676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda", "start_char": 0, "end_char": 2200, "text_sha256": "773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda"}
experimental_model
Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells
exposure
D- and L-ibuprofen and flurbiprofen tested against the mutant panel
limitations
Identifies which residue does the stereochemical discrimination by changing it and watching the discrimination collapse. Ovine recombinant enzyme.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Sheep enzyme
plain_language
A single arginine grips the acid group of both the substrate and the drug, and without it the slow kind of inhibition cannot happen.
primary_references
[ibu-p8567676] Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. (1996). https://pubmed.ncbi.nlm.nih.gov/8567676/ DOI: 10.1074/jbc.271.4.2179
tissue_or_cell_type
Recombinant cyclooxygenase-1
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 253–264
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells · source_derived_draft · unverified_draft
### ibu-arg120-anchors-the-carboxylate All mutants retained at least part of their activity except R120E which had none, Km values for arachidonic acid were 87 and 3300 micromolar for R120K and R120Q against 4 micromolar for native enzyme, and the R120Q mutant failed to undergo suicide inactivation during catalysis or time-dependent inhibition by flurbiprofen, results consistent with Arg120 binding the carboxylate group of arachidonate and indicating that interaction of the carboxylate of substrates and inhibitors with Arg120 is necessary for suicide inactivation and time-dependent inhibition respectively; Glu524 substitutions did not significantly change Km. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: A single arginine grips the acid group of both the substrate and the drug, and without it the slow kind of inhibition cannot happen. organism: Sheep enzyme tissue_or_cell_type: Recombinant cyclooxygenase-1 experimental_model: Site-directed mutants of ovine cyclooxygenase-1 at Arg120, Glu524 and Tyr355 expressed in COS-1 cells limitations: Identifies which residue does the stereochemical discrimination by changing it and watching the discrimination collapse. Ovine recombinant enzyme. exposure: D- and L-ibuprofen and flurbiprofen tested against the mutant panel evidence_span: {"source_cache": "artifacts/ibuprofen-research/8567676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda", "start_char": 0, "end_char": 2200, "text_sha256": "773dc61cda18ae93ea7dfaf128870c2c5926fb828d7a1563f413e97e29893eda"} [ibu-p8567676] Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1. (1996). https://pubmed.ncbi.nlm.nih.gov/8567676/ DOI: 10.1074/jbc.271.4.2179
Complete structured claim and evidence
Conversion of the carboxylate moiety of flurbiprofen to an ester or amide abolishes slow tight-binding behaviour regardless of halogenation state, and contrary to prior predictions a halogen substituent is not sufficient to confer slow tight-binding behaviour.
The free carboxylate group of a 2-arylpropionic acid inhibitor → Time-dependent, slowly reversible inhibition of cyclooxygenase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/14741265.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "244b7634bca0e2a090e86f49257289d02d19637b2c540260e94662dcdaa4111a", "start_char": 0, "end_char": 405, "text_sha256": "244b7634bca0e2a090e86f49257289d02d19637b2c540260e94662dcdaa4111a"}
experimental_model
Chemical modification of flurbiprofen and ibuprofen to alter cyclooxygenase-1 binding kinetics
exposure
Halogenated and carboxylate-modified analogues tested for slow tight-binding behaviour
limitations
A structure-activity result on the kinetic class of inhibition rather than on potency. It does not report the potencies themselves.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Enzyme
plain_language
Cap the acid group and the drug can no longer settle into the slow, tenacious kind of binding.
primary_references
[ibu-p14741265] Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors. (2004). https://pubmed.ncbi.nlm.nih.gov/14741265/ DOI: 10.1016/j.bmcl.2003.11.034
tissue_or_cell_type
Cyclooxygenase-1
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 266–277
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical modification of flurbiprofen and ibuprofen to alter cyclooxygenase-1 binding kinetics · source_derived_draft · unverified_draft
### ibu-the-free-acid-is-required Conversion of the carboxylate moiety of flurbiprofen to an ester or amide abolishes slow tight-binding behaviour regardless of halogenation state, and contrary to prior predictions a halogen substituent is not sufficient to confer slow tight-binding behaviour. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Cap the acid group and the drug can no longer settle into the slow, tenacious kind of binding. organism: Enzyme tissue_or_cell_type: Cyclooxygenase-1 experimental_model: Chemical modification of flurbiprofen and ibuprofen to alter cyclooxygenase-1 binding kinetics limitations: A structure-activity result on the kinetic class of inhibition rather than on potency. It does not report the potencies themselves. exposure: Halogenated and carboxylate-modified analogues tested for slow tight-binding behaviour evidence_span: {"source_cache": "artifacts/ibuprofen-research/14741265.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "244b7634bca0e2a090e86f49257289d02d19637b2c540260e94662dcdaa4111a", "start_char": 0, "end_char": 405, "text_sha256": "244b7634bca0e2a090e86f49257289d02d19637b2c540260e94662dcdaa4111a"} [ibu-p14741265] Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors. (2004). https://pubmed.ncbi.nlm.nih.gov/14741265/ DOI: 10.1016/j.bmcl.2003.11.034
Complete structured claim and evidence
When platelets were isolated and resuspended in homologous drug-free plasma, slow recovery of thromboxane production was seen after indomethacin with 50% of control activity regained in 100 minutes, whereas ibuprofen-treated platelets, exposed to a competitive inhibitor of cyclooxygenase, recovered nearly completely immediately on being resuspended in drug-free plasma.
Ibuprofen → Reversible, competitive inhibition of cyclooxygenase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/3088675.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee49ae775f6c268fd63afc816cda206f0bdab5efe9ce86b4f97fd8ee6bda3a1a", "start_char": 0, "end_char": 1400, "text_sha256": "ee49ae775f6c268fd63afc816cda206f0bdab5efe9ce86b4f97fd8ee6bda3a1a"}
experimental_model
Kinetics of recovery of platelet thromboxane production after single doses, with platelets resuspended in drug-free plasma
exposure
Indomethacin and ibuprofen compared, with isolated platelets and platelet microsomes
limitations
The resuspension experiment is what separates a reversible inhibitor from a slowly reversible one. It uses indomethacin as the contrast and reports ibuprofen as the reference reversible drug.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
Wash the drug away and the platelet enzyme is working again at once, which is the opposite of what aspirin does.
primary_references
[ibu-p3088675] Time-dependent inhibition of platelet cyclooxygenase by indomethacin is slowly reversible. (1986). https://pubmed.ncbi.nlm.nih.gov/3088675/ DOI: 10.1016/0090-6980(86)90170-x
tissue_or_cell_type
Platelets
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 279–290
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics of recovery of platelet thromboxane production after single doses, with platelets resuspended in drug-free plasma · source_derived_draft · unverified_draft
### ibu-ibuprofen-washes-straight-out When platelets were isolated and resuspended in homologous drug-free plasma, slow recovery of thromboxane production was seen after indomethacin with 50% of control activity regained in 100 minutes, whereas ibuprofen-treated platelets, exposed to a competitive inhibitor of cyclooxygenase, recovered nearly completely immediately on being resuspended in drug-free plasma. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Wash the drug away and the platelet enzyme is working again at once, which is the opposite of what aspirin does. organism: Human tissue_or_cell_type: Platelets experimental_model: Kinetics of recovery of platelet thromboxane production after single doses, with platelets resuspended in drug-free plasma limitations: The resuspension experiment is what separates a reversible inhibitor from a slowly reversible one. It uses indomethacin as the contrast and reports ibuprofen as the reference reversible drug. exposure: Indomethacin and ibuprofen compared, with isolated platelets and platelet microsomes evidence_span: {"source_cache": "artifacts/ibuprofen-research/3088675.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee49ae775f6c268fd63afc816cda206f0bdab5efe9ce86b4f97fd8ee6bda3a1a", "start_char": 0, "end_char": 1400, "text_sha256": "ee49ae775f6c268fd63afc816cda206f0bdab5efe9ce86b4f97fd8ee6bda3a1a"} [ibu-p3088675] Time-dependent inhibition of platelet cyclooxygenase by indomethacin is slowly reversible. (1986). https://pubmed.ncbi.nlm.nih.gov/3088675/ DOI: 10.1016/0090-6980(86)90170-x
Complete structured claim and evidence
Reversible inhibition of both cellular cyclooxygenase-1 and cyclooxygenase-2 was observed with the nonselective drugs ibuprofen and indomethacin, whereas the selective inhibitor DuP-697 was reversible against cyclooxygenase-1 but irreversible against cyclooxygenase-2, and indomethacin displayed time-dependent inhibition of both cellular isoforms; the selectivities and potencies of inhibitors determined using intact cells are affected by substrate concentration and differ from those determined in cell-free microsomal or purified enzyme preparations.
Ibuprofen → Cyclooxygenase-2 (PTGS2) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/8831731.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3161aac692f44c874cafb498e9606f0382b380662ccb58cd1683139f1c1df99", "start_char": 0, "end_char": 1993, "text_sha256": "d3161aac692f44c874cafb498e9606f0382b380662ccb58cd1683139f1c1df99"}
experimental_model
Chinese hamster ovary cell lines stably expressing each human cyclooxygenase isoform, with cell-free comparison
exposure
Ibuprofen, indomethacin, NS-398 and DuP-697 across intact cells and microsomal preparations
limitations
Shows that the selectivity numbers depend on the assay, which bears on every potency ratio quoted for this drug class. A heterologous expression system.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human enzyme in hamster cells
plain_language
Against both enzymes it is a reversible blocker, and the numbers you get depend on which assay you use.
primary_references
[ibu-p8831731] Mechanism of selective inhibition of human prostaglandin G/H synthase-1 and -2 in intact cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8831731/ DOI: 10.1016/0006-2952(96)00462-5
tissue_or_cell_type
Intact cells and cell-free preparations
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 292–303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chinese hamster ovary cell lines stably expressing each human cyclooxygenase isoform, with cell-free comparison · source_derived_draft · unverified_draft
### ibu-reversible-against-both-isoforms Reversible inhibition of both cellular cyclooxygenase-1 and cyclooxygenase-2 was observed with the nonselective drugs ibuprofen and indomethacin, whereas the selective inhibitor DuP-697 was reversible against cyclooxygenase-1 but irreversible against cyclooxygenase-2, and indomethacin displayed time-dependent inhibition of both cellular isoforms; the selectivities and potencies of inhibitors determined using intact cells are affected by substrate concentration and differ from those determined in cell-free microsomal or purified enzyme preparations. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Against both enzymes it is a reversible blocker, and the numbers you get depend on which assay you use. organism: Human enzyme in hamster cells tissue_or_cell_type: Intact cells and cell-free preparations experimental_model: Chinese hamster ovary cell lines stably expressing each human cyclooxygenase isoform, with cell-free comparison limitations: Shows that the selectivity numbers depend on the assay, which bears on every potency ratio quoted for this drug class. A heterologous expression system. exposure: Ibuprofen, indomethacin, NS-398 and DuP-697 across intact cells and microsomal preparations evidence_span: {"source_cache": "artifacts/ibuprofen-research/8831731.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3161aac692f44c874cafb498e9606f0382b380662ccb58cd1683139f1c1df99", "start_char": 0, "end_char": 1993, "text_sha256": "d3161aac692f44c874cafb498e9606f0382b380662ccb58cd1683139f1c1df99"} [ibu-p8831731] Mechanism of selective inhibition of human prostaglandin G/H synthase-1 and -2 in intact cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8831731/ DOI: 10.1016/0006-2952(96)00462-5
Complete structured claim and evidence
Native ovine cyclooxygenase-1 produced primarily prostaglandin G2 along with 11R-, 15S- and 15R-hydroxyeicosatetraenoic acids with different Km values for each product, establishing that arachidonate can assume at least three catalytically productive arrangements within the site, and half-maximal inhibitory concentrations for the competitive inhibitor ibuprofen were the same for every product of a given enzyme form, 175 micromolar for the native enzyme and 15 micromolar for the V349L mutant, most simply rationalised by a model in which arachidonate forms its various arrangements only after entering the cyclooxygenase active site.
Ibuprofen → The profile of prostaglandin G2 and monohydroxy acid products of cyclooxygenase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/10722687.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8e9ebedd8a4d791246c951376fa2f6f07a5ca8af828bafd15836bec26c090348", "start_char": 0, "end_char": 2063, "text_sha256": "8e9ebedd8a4d791246c951376fa2f6f07a5ca8af828bafd15836bec26c090348"}
experimental_model
Product analysis and kinetics for solubilised, membrane-associated and active-site-mutant ovine cyclooxygenase-1
exposure
Arachidonate product profiling with ibuprofen as a competitive inhibitor
limitations
The identical inhibitory concentration across three different products is the informative result. The concentrations are high and the enzyme is ovine.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Sheep enzyme
plain_language
The drug blocks the door rather than any one position inside, which is why it stops every product equally.
primary_references
[ibu-p10722687] Different catalytically competent arrangements of arachidonic acid within the cyclooxygenase active site of prostaglandin endoperoxide H synthase-1 lead to the formation of different oxygenated products. (2000). https://pubmed.ncbi.nlm.nih.gov/10722687/ DOI: 10.1074/jbc.275.12.8501
tissue_or_cell_type
Cyclooxygenase-1
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 305–316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product analysis and kinetics for solubilised, membrane-associated and active-site-mutant ovine cyclooxygenase-1 · source_derived_draft · unverified_draft
### ibu-blocks-entry-not-orientation Native ovine cyclooxygenase-1 produced primarily prostaglandin G2 along with 11R-, 15S- and 15R-hydroxyeicosatetraenoic acids with different Km values for each product, establishing that arachidonate can assume at least three catalytically productive arrangements within the site, and half-maximal inhibitory concentrations for the competitive inhibitor ibuprofen were the same for every product of a given enzyme form, 175 micromolar for the native enzyme and 15 micromolar for the V349L mutant, most simply rationalised by a model in which arachidonate forms its various arrangements only after entering the cyclooxygenase active site. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The drug blocks the door rather than any one position inside, which is why it stops every product equally. organism: Sheep enzyme tissue_or_cell_type: Cyclooxygenase-1 experimental_model: Product analysis and kinetics for solubilised, membrane-associated and active-site-mutant ovine cyclooxygenase-1 limitations: The identical inhibitory concentration across three different products is the informative result. The concentrations are high and the enzyme is ovine. exposure: Arachidonate product profiling with ibuprofen as a competitive inhibitor evidence_span: {"source_cache": "artifacts/ibuprofen-research/10722687.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8e9ebedd8a4d791246c951376fa2f6f07a5ca8af828bafd15836bec26c090348", "start_char": 0, "end_char": 2063, "text_sha256": "8e9ebedd8a4d791246c951376fa2f6f07a5ca8af828bafd15836bec26c090348"} [ibu-p10722687] Different catalytically competent arrangements of arachidonic acid within the cyclooxygenase active site of prostaglandin endoperoxide H synthase-1 lead to the formation of different oxygenated products. (2000). https://pubmed.ncbi.nlm.nih.gov/10722687/ DOI: 10.1074/jbc.275.12.8501
Complete structured claim and evidence
The S(+) isomer of ibuprofen was 32-, 41- and 96-fold more potent than the R(-) isomer for inhibition of prostaglandin endoperoxide H synthase-1 activity, human platelet aggregation and serotonin secretion respectively, while on prostaglandin endoperoxide H synthase-2 the ibuprofen isomers showed no selectivity, and indomethacin, S(+)-ibuprofen and S(+)-naproxen were 6-, 27- and 5-fold more potent as inhibitors of synthase-1 than of synthase-2.
S(+)-ibuprofen → R(-)-ibuprofen source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts
exposure
S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation
limitations
The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat, human and sheep systems
plain_language
At the first enzyme one hand is thirty to ninety times stronger; at the second enzyme the two hands are indistinguishable.
primary_references
[ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x
tissue_or_cell_type
Transfected cells, hepatoma cells, platelets and purified enzyme
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 318–329
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts · source_derived_draft · unverified_draft
### ibu-thirty-two-fold-at-cox1 The S(+) isomer of ibuprofen was 32-, 41- and 96-fold more potent than the R(-) isomer for inhibition of prostaglandin endoperoxide H synthase-1 activity, human platelet aggregation and serotonin secretion respectively, while on prostaglandin endoperoxide H synthase-2 the ibuprofen isomers showed no selectivity, and indomethacin, S(+)-ibuprofen and S(+)-naproxen were 6-, 27- and 5-fold more potent as inhibitors of synthase-1 than of synthase-2. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: At the first enzyme one hand is thirty to ninety times stronger; at the second enzyme the two hands are indistinguishable. organism: Rat, human and sheep systems tissue_or_cell_type: Transfected cells, hepatoma cells, platelets and purified enzyme experimental_model: Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts limitations: The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined. exposure: S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"} [ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x
Complete structured claim and evidence
Each drug tested produced concentration-dependent activation of peroxisome proliferator-activated receptor alpha and gamma isoforms and of peroxisomal fatty acyl-CoA beta-oxidase activity, with a rank order of stereoselectivity for alpha activation and fatty acyl oxidase stimulation of S(+)-ibuprofen greater than R(-)-ibuprofen, S(+)-ibuprofen being more potent than indomethacin and naproxen on these parameters, while on gamma the order was S(+)-naproxen greater than indomethacin greater than S(+)-ibuprofen greater than R(-)-ibuprofen.
S(+)-ibuprofen → Human PPAR alpha / PPARA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"}
experimental_model
Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts
exposure
S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation
limitations
The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat, human and sheep systems
plain_language
Both hands switch on the fat-handling nuclear receptors, with a much smaller gap between them than at cyclooxygenase.
primary_references
[ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x
tissue_or_cell_type
Transfected cells, hepatoma cells, platelets and purified enzyme
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 331–342
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts · source_derived_draft · unverified_draft
### ibu-both-isomers-hit-ppar Each drug tested produced concentration-dependent activation of peroxisome proliferator-activated receptor alpha and gamma isoforms and of peroxisomal fatty acyl-CoA beta-oxidase activity, with a rank order of stereoselectivity for alpha activation and fatty acyl oxidase stimulation of S(+)-ibuprofen greater than R(-)-ibuprofen, S(+)-ibuprofen being more potent than indomethacin and naproxen on these parameters, while on gamma the order was S(+)-naproxen greater than indomethacin greater than S(+)-ibuprofen greater than R(-)-ibuprofen. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Both hands switch on the fat-handling nuclear receptors, with a much smaller gap between them than at cyclooxygenase. organism: Rat, human and sheep systems tissue_or_cell_type: Transfected cells, hepatoma cells, platelets and purified enzyme experimental_model: Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts limitations: The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined. exposure: S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"} [ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x
Complete structured claim and evidence
Measurement of the inhibitory potency of non-steroidal anti-inflammatory drugs on cyclooxygenase isoforms is strongly influenced by variations in experimental conditions, the concentration of protein in the assay medium being particularly important because these drugs are highly protein bound in vivo so that assays based on human whole blood provide the most suitable test system, and of the drugs investigated only meloxicam showed selectivity for cyclooxygenase-2 at therapeutically relevant concentrations while standard drugs such as naproxen inhibited both isoforms to an equal degree.
The human whole blood assay of cyclooxygenase activity → The ratio of cyclooxygenase-1 to cyclooxygenase-2 inhibitory potency source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/9219317.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714", "start_char": 0, "end_char": 1162, "text_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714"}
experimental_model
Comparison of cyclooxygenase inhibitory potency across assay systems, using the human whole blood assay
exposure
Standard non-steroidal anti-inflammatory drugs compared at therapeutically relevant concentrations
limitations
Argues that the whole blood assay is the appropriate test because these drugs are highly protein bound. It reports conclusions about the class, with naproxen named rather than ibuprofen.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
Measured in blood rather than in a tube of enzyme, the ordinary anti-inflammatories hit both enzymes about equally.
primary_references
[ibu-p9219317] Differentiating among nonsteroidal antiinflammatory drugs by pharmacokinetic and pharmacodynamic profiles. (1997). https://pubmed.ncbi.nlm.nih.gov/9219317/ DOI: 10.1016/s0049-0172(97)80050-9
tissue_or_cell_type
Whole blood
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 344–355
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparison of cyclooxygenase inhibitory potency across assay systems, using the human whole blood assay · source_derived_draft · unverified_draft
### ibu-no-selectivity-in-whole-blood Measurement of the inhibitory potency of non-steroidal anti-inflammatory drugs on cyclooxygenase isoforms is strongly influenced by variations in experimental conditions, the concentration of protein in the assay medium being particularly important because these drugs are highly protein bound in vivo so that assays based on human whole blood provide the most suitable test system, and of the drugs investigated only meloxicam showed selectivity for cyclooxygenase-2 at therapeutically relevant concentrations while standard drugs such as naproxen inhibited both isoforms to an equal degree. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Measured in blood rather than in a tube of enzyme, the ordinary anti-inflammatories hit both enzymes about equally. organism: Human tissue_or_cell_type: Whole blood experimental_model: Comparison of cyclooxygenase inhibitory potency across assay systems, using the human whole blood assay limitations: Argues that the whole blood assay is the appropriate test because these drugs are highly protein bound. It reports conclusions about the class, with naproxen named rather than ibuprofen. exposure: Standard non-steroidal anti-inflammatory drugs compared at therapeutically relevant concentrations evidence_span: {"source_cache": "artifacts/ibuprofen-research/9219317.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714", "start_char": 0, "end_char": 1162, "text_sha256": "d3edafe44ec9bf9e15505ffebb96add5467f8874fe8b585ce3878c473f250714"} [ibu-p9219317] Differentiating among nonsteroidal antiinflammatory drugs by pharmacokinetic and pharmacodynamic profiles. (1997). https://pubmed.ncbi.nlm.nih.gov/9219317/ DOI: 10.1016/s0049-0172(97)80050-9
Complete structured claim and evidence
Incubation of human mononuclear cells with lipopolysaccharide induced a time-dependent increase in cyclooxygenase-2 protein of more than a hundredfold at 24 hours with increased prostaglandin E2 production, while cyclooxygenase-1 protein was present at time zero and not induced, and most non-steroidal anti-inflammatory drugs are more potent at inhibiting cyclooxygenase-1 than cyclooxygenase-2, with five experimental compounds showing greater selectivity for cyclooxygenase-2.
Cyclooxygenase-1 (PTGS1) → Ibuprofen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/8907587.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99f3a26e6399b5f81c18859b9f62eafcd7aa6fc4e483d97a39e8c35c060a9d75", "start_char": 0, "end_char": 1101, "text_sha256": "99f3a26e6399b5f81c18859b9f62eafcd7aa6fc4e483d97a39e8c35c060a9d75"}
experimental_model
Lipopolysaccharide-challenged human whole blood with prostaglandin E2 and thromboxane B2 as isoform indices
exposure
Lipopolysaccharide induction of cyclooxygenase-2 with a single oral indomethacin dose ex vivo
limitations
Establishes the assay the other records rely on. Indomethacin rather than ibuprofen is the drug dosed here.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
The first enzyme is always there and the second one appears when tissue is provoked; most of these drugs hit the first harder.
primary_references
[ibu-p8907587] A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. (1996). https://pubmed.ncbi.nlm.nih.gov/8907587/ DOI: 10.1007/bf02265118
tissue_or_cell_type
Whole blood and mononuclear cells
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 357–368
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lipopolysaccharide-challenged human whole blood with prostaglandin E2 and thromboxane B2 as isoform indices · source_derived_draft · unverified_draft
### ibu-most-nsaids-favour-cox1 Incubation of human mononuclear cells with lipopolysaccharide induced a time-dependent increase in cyclooxygenase-2 protein of more than a hundredfold at 24 hours with increased prostaglandin E2 production, while cyclooxygenase-1 protein was present at time zero and not induced, and most non-steroidal anti-inflammatory drugs are more potent at inhibiting cyclooxygenase-1 than cyclooxygenase-2, with five experimental compounds showing greater selectivity for cyclooxygenase-2. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The first enzyme is always there and the second one appears when tissue is provoked; most of these drugs hit the first harder. organism: Human tissue_or_cell_type: Whole blood and mononuclear cells experimental_model: Lipopolysaccharide-challenged human whole blood with prostaglandin E2 and thromboxane B2 as isoform indices limitations: Establishes the assay the other records rely on. Indomethacin rather than ibuprofen is the drug dosed here. exposure: Lipopolysaccharide induction of cyclooxygenase-2 with a single oral indomethacin dose ex vivo evidence_span: {"source_cache": "artifacts/ibuprofen-research/8907587.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99f3a26e6399b5f81c18859b9f62eafcd7aa6fc4e483d97a39e8c35c060a9d75", "start_char": 0, "end_char": 1101, "text_sha256": "99f3a26e6399b5f81c18859b9f62eafcd7aa6fc4e483d97a39e8c35c060a9d75"} [ibu-p8907587] A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. (1996). https://pubmed.ncbi.nlm.nih.gov/8907587/ DOI: 10.1007/bf02265118
Complete structured claim and evidence
R(-)-ibuprofen with a half-maximal inhibitory concentration of 121.8 micromolar and S(+)-ibuprofen at 61.7 micromolar both inhibited activation of nuclear factor kappa B in response to T-cell stimulation, the effect was specific in that ibuprofen up to 10 millimolar did not affect heat shock transcription factor or activation by prostaglandin E2, concentrations of 20 millimolar did not prevent binding to DNA in vitro, and immunofluorescence and nuclear import experiments indicate the site of action is upstream of dissociation of the nuclear factor kappa B-I-kappa-B complex; only the S(+) enantiomer is an effective cyclooxygenase inhibitor, so the mechanism by which R(-) exerts anti-inflammatory and antinociceptive effects remains unknown.
R(-)-ibuprofen → Activation of nuclear factor kappa B in response to T-cell stimulation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/9517383.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a3938a95448a472769fdce1c05ac55d853bfdbdbcda7554ec5b79dcb423db35", "start_char": 0, "end_char": 1478, "text_sha256": "7a3938a95448a472769fdce1c05ac55d853bfdbdbcda7554ec5b79dcb423db35"}
experimental_model
Electrophoretic mobility-shift assays, transient transfection, confocal immunofluorescence and nuclear import experiments
exposure
R(-)- and S(+)-ibuprofen compared as inhibitors of nuclear factor kappa B activation
limitations
Compares the enantiomers on a target where the cyclooxygenase argument does not apply. The concentrations are high, in the tens to hundreds of micromolar.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human cells
plain_language
On this target the two hands are only twofold apart, not thirty, which is a route by which the so-called inactive one could work.
primary_references
[ibu-p9517383] Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen. (1998). https://pubmed.ncbi.nlm.nih.gov/9517383/ DOI: 10.1038/sj.bjp.0701652
tissue_or_cell_type
T lymphocytes
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 370–381
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophoretic mobility-shift assays, transient transfection, confocal immunofluorescence and nuclear import experiments · source_derived_draft · unverified_draft
### ibu-both-hands-block-nfkb R(-)-ibuprofen with a half-maximal inhibitory concentration of 121.8 micromolar and S(+)-ibuprofen at 61.7 micromolar both inhibited activation of nuclear factor kappa B in response to T-cell stimulation, the effect was specific in that ibuprofen up to 10 millimolar did not affect heat shock transcription factor or activation by prostaglandin E2, concentrations of 20 millimolar did not prevent binding to DNA in vitro, and immunofluorescence and nuclear import experiments indicate the site of action is upstream of dissociation of the nuclear factor kappa B-I-kappa-B complex; only the S(+) enantiomer is an effective cyclooxygenase inhibitor, so the mechanism by which R(-) exerts anti-inflammatory and antinociceptive effects remains unknown. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: On this target the two hands are only twofold apart, not thirty, which is a route by which the so-called inactive one could work. organism: Human cells tissue_or_cell_type: T lymphocytes experimental_model: Electrophoretic mobility-shift assays, transient transfection, confocal immunofluorescence and nuclear import experiments limitations: Compares the enantiomers on a target where the cyclooxygenase argument does not apply. The concentrations are high, in the tens to hundreds of micromolar. exposure: R(-)- and S(+)-ibuprofen compared as inhibitors of nuclear factor kappa B activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/9517383.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a3938a95448a472769fdce1c05ac55d853bfdbdbcda7554ec5b79dcb423db35", "start_char": 0, "end_char": 1478, "text_sha256": "7a3938a95448a472769fdce1c05ac55d853bfdbdbcda7554ec5b79dcb423db35"} [ibu-p9517383] Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal drug ibuprofen. (1998). https://pubmed.ncbi.nlm.nih.gov/9517383/ DOI: 10.1038/sj.bjp.0701652
Complete structured claim and evidence
Ibuprofen, indomethacin and sulindac sulphide preferentially decreased the highly amyloidogenic amyloid-beta 42 peptide produced by a variety of cultured cells by as much as 80%, an effect not seen with all non-steroidal anti-inflammatory drugs and seemingly not mediated by inhibition of cyclooxygenase activity, and short-term administration of ibuprofen to mice producing mutant amyloid precursor protein lowered brain amyloid-beta 42; in cultured cells the decrease was accompanied by an increase in the amyloid-beta 1-38 isoform, indicating that these drugs subtly alter gamma-secretase activity without significantly perturbing other processing pathways or Notch cleavage.
Ibuprofen → Amyloid-beta 42, the 42-residue isoform source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/11700559.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb9be6e821c04b48c65a999ac5852996bcb4f0249b8bd78b4454a256435e8267", "start_char": 0, "end_char": 1411, "text_sha256": "eb9be6e821c04b48c65a999ac5852996bcb4f0249b8bd78b4454a256435e8267"}
experimental_model
Cultured cells of several types and mutant amyloid precursor protein transgenic mice
exposure
Ibuprofen, indomethacin and sulindac sulphide, with short-term ibuprofen administration in vivo
limitations
The cyclooxygenase-independence is inferred from the fact that the effect is not shared by all inhibitors of the enzyme, rather than shown by a genetic control. Short-term dosing in a transgenic model.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human cells and mouse
plain_language
The drug shifts where an enzyme cuts rather than stopping it, and the sticky fragment is replaced by a shorter harmless one.
primary_references
[ibu-p11700559] A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. (2001). https://pubmed.ncbi.nlm.nih.gov/11700559/ DOI: 10.1038/35102591
tissue_or_cell_type
Cultured cells and brain
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 383–394
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured cells of several types and mutant amyloid precursor protein transgenic mice · source_derived_draft · unverified_draft
### ibu-lowers-abeta42-not-via-cox Ibuprofen, indomethacin and sulindac sulphide preferentially decreased the highly amyloidogenic amyloid-beta 42 peptide produced by a variety of cultured cells by as much as 80%, an effect not seen with all non-steroidal anti-inflammatory drugs and seemingly not mediated by inhibition of cyclooxygenase activity, and short-term administration of ibuprofen to mice producing mutant amyloid precursor protein lowered brain amyloid-beta 42; in cultured cells the decrease was accompanied by an increase in the amyloid-beta 1-38 isoform, indicating that these drugs subtly alter gamma-secretase activity without significantly perturbing other processing pathways or Notch cleavage. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The drug shifts where an enzyme cuts rather than stopping it, and the sticky fragment is replaced by a shorter harmless one. organism: Human cells and mouse tissue_or_cell_type: Cultured cells and brain experimental_model: Cultured cells of several types and mutant amyloid precursor protein transgenic mice limitations: The cyclooxygenase-independence is inferred from the fact that the effect is not shared by all inhibitors of the enzyme, rather than shown by a genetic control. Short-term dosing in a transgenic model. exposure: Ibuprofen, indomethacin and sulindac sulphide, with short-term ibuprofen administration in vivo evidence_span: {"source_cache": "artifacts/ibuprofen-research/11700559.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb9be6e821c04b48c65a999ac5852996bcb4f0249b8bd78b4454a256435e8267", "start_char": 0, "end_char": 1411, "text_sha256": "eb9be6e821c04b48c65a999ac5852996bcb4f0249b8bd78b4454a256435e8267"} [ibu-p11700559] A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. (2001). https://pubmed.ncbi.nlm.nih.gov/11700559/ DOI: 10.1038/35102591
Complete structured claim and evidence
R-ibuprofen and R-flurbiprofen, with poor cyclooxygenase-inhibiting activity, reduce amyloid-beta 42 production by human cells, and although these R enantiomers inhibit nuclear factor kappa B activation and that factor can selectively regulate amyloid-beta 42, the reduction is not mediated by inhibition of nuclear factor kappa B activation; clinical use of these drugs for Alzheimer’s disease has been hampered by dose-limiting toxicity believed to be due to cyclooxygenase inhibition, which is reportedly not essential for selective amyloid-beta 42 reduction.
R(-)-ibuprofen → Amyloid-beta 42, the 42-residue isoform source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/12421374.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb022923aad1deb90ae4c540e3e8aab4080a3b78aa9c4a9356447385c31e9c8b", "start_char": 0, "end_char": 1003, "text_sha256": "bb022923aad1deb90ae4c540e3e8aab4080a3b78aa9c4a9356447385c31e9c8b"}
experimental_model
Human cells treated with single enantiomers of ibuprofen and flurbiprofen
exposure
R-ibuprofen and R-flurbiprofen, chosen for their poor cyclooxygenase-inhibiting activity
limitations
Uses the enantiomer as the control for cyclooxygenase involvement, which is cleaner than comparing different drugs. It also rules out the nuclear factor kappa B route explicitly.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human cells
plain_language
The half of the molecule that cannot block cyclooxygenase is the half that lowers the Alzheimer peptide.
primary_references
[ibu-p12421374] Selective inhibition of Abeta42 production by NSAID R-enantiomers. (2002). https://pubmed.ncbi.nlm.nih.gov/12421374/ DOI: 10.1046/j.1471-4159.2002.01195.x
tissue_or_cell_type
Cultured cells
trigger_kind
biomarker_context Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 396–407
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cells treated with single enantiomers of ibuprofen and flurbiprofen · source_derived_draft · unverified_draft
### ibu-r-enantiomer-lowers-abeta42 R-ibuprofen and R-flurbiprofen, with poor cyclooxygenase-inhibiting activity, reduce amyloid-beta 42 production by human cells, and although these R enantiomers inhibit nuclear factor kappa B activation and that factor can selectively regulate amyloid-beta 42, the reduction is not mediated by inhibition of nuclear factor kappa B activation; clinical use of these drugs for Alzheimer’s disease has been hampered by dose-limiting toxicity believed to be due to cyclooxygenase inhibition, which is reportedly not essential for selective amyloid-beta 42 reduction. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The half of the molecule that cannot block cyclooxygenase is the half that lowers the Alzheimer peptide. organism: Human cells tissue_or_cell_type: Cultured cells experimental_model: Human cells treated with single enantiomers of ibuprofen and flurbiprofen limitations: Uses the enantiomer as the control for cyclooxygenase involvement, which is cleaner than comparing different drugs. It also rules out the nuclear factor kappa B route explicitly. exposure: R-ibuprofen and R-flurbiprofen, chosen for their poor cyclooxygenase-inhibiting activity evidence_span: {"source_cache": "artifacts/ibuprofen-research/12421374.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb022923aad1deb90ae4c540e3e8aab4080a3b78aa9c4a9356447385c31e9c8b", "start_char": 0, "end_char": 1003, "text_sha256": "bb022923aad1deb90ae4c540e3e8aab4080a3b78aa9c4a9356447385c31e9c8b"} [ibu-p12421374] Selective inhibition of Abeta42 production by NSAID R-enantiomers. (2002). https://pubmed.ncbi.nlm.nih.gov/12421374/ DOI: 10.1046/j.1471-4159.2002.01195.x
Complete structured claim and evidence
Sulindac sulfide directly acts on gamma-secretase and preferentially inhibits the activity generating amyloid-beta 42 from solubilised membrane fractions in an in vitro assay using recombinant amyloid precursor protein C100 as substrate, also inhibiting generation of amyloid-beta 40 and of the Notch intracellular domain at higher concentrations, and displaying linear noncompetitive inhibition profiles for the amyloid-beta 42 generating activity.
Sulindac sulfide, the active metabolite of sulindac → The gamma-secretase complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/12637581.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0da78f88f2dfa34808abab5f1d223bdbc0372f5ea26a626b9697e0ad2255a7c", "start_char": 0, "end_char": 1209, "text_sha256": "e0da78f88f2dfa34808abab5f1d223bdbc0372f5ea26a626b9697e0ad2255a7c"}
experimental_model
In vitro gamma-secretase assay on solubilised HeLa membrane fractions with recombinant amyloid precursor protein C100
exposure
Sulindac sulfide applied to isolated gamma-secretase activity
limitations
A cell-free assay that can distinguish direct action on the enzyme from an effect on the cell. It tests sulindac sulfide rather than ibuprofen, which is recorded on the claim.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human cells
plain_language
Taken out of the cell entirely, the drug still acts on the enzyme itself, and prefers the reaction that makes the harmful fragment.
primary_references
[ibu-p12637581] Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation. (2003). https://pubmed.ncbi.nlm.nih.gov/12637581/ DOI: 10.1074/jbc.m301619200
tissue_or_cell_type
Solubilised membrane fractions
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 409–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vitro gamma-secretase assay on solubilised HeLa membrane fractions with recombinant amyloid precursor protein C100 · source_derived_draft · unverified_draft
### ibu-direct-on-gamma-secretase Sulindac sulfide directly acts on gamma-secretase and preferentially inhibits the activity generating amyloid-beta 42 from solubilised membrane fractions in an in vitro assay using recombinant amyloid precursor protein C100 as substrate, also inhibiting generation of amyloid-beta 40 and of the Notch intracellular domain at higher concentrations, and displaying linear noncompetitive inhibition profiles for the amyloid-beta 42 generating activity. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Taken out of the cell entirely, the drug still acts on the enzyme itself, and prefers the reaction that makes the harmful fragment. organism: Human cells tissue_or_cell_type: Solubilised membrane fractions experimental_model: In vitro gamma-secretase assay on solubilised HeLa membrane fractions with recombinant amyloid precursor protein C100 limitations: A cell-free assay that can distinguish direct action on the enzyme from an effect on the cell. It tests sulindac sulfide rather than ibuprofen, which is recorded on the claim. exposure: Sulindac sulfide applied to isolated gamma-secretase activity evidence_span: {"source_cache": "artifacts/ibuprofen-research/12637581.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0da78f88f2dfa34808abab5f1d223bdbc0372f5ea26a626b9697e0ad2255a7c", "start_char": 0, "end_char": 1209, "text_sha256": "e0da78f88f2dfa34808abab5f1d223bdbc0372f5ea26a626b9697e0ad2255a7c"} [ibu-p12637581] Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation. (2003). https://pubmed.ncbi.nlm.nih.gov/12637581/ DOI: 10.1074/jbc.m301619200
Complete structured claim and evidence
Ibuprofen activates peroxisome proliferator-activated receptor gamma in neuron-like PC12 and B104 cells, activation with traditional agonists mimics the RhoA-inhibiting properties of ibuprofen and promotes neurite elongation in primary neurons exposed to axonal growth inhibitors, small interfering RNA against the receptor blocks RhoA suppression by those agonists, and selective receptor inhibition prevents the effect of ibuprofen on RhoA activity and neurite growth, supporting an essential role for the receptor in coupling ibuprofen to RhoA inhibition.
Human PPAR gamma / PPARG → RhoA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/20089905.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77e2dbb010dcee44bd66645ec26cb844d7041ea4930f6373ae5dd6b10da37df3", "start_char": 0, "end_char": 1812, "text_sha256": "77e2dbb010dcee44bd66645ec26cb844d7041ea4930f6373ae5dd6b10da37df3"}
experimental_model
Neuron-like PC12 and B104 cells and primary cultured neurons with small interfering RNA knockdown
exposure
Ibuprofen with peroxisome proliferator-activated receptor gamma agonists, antagonists and knockdown
limitations
The knockdown and the selective antagonist together make the receptor requirement a test rather than a correlation. Cell lines and primary culture rather than an animal.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
The drug reaches a growth-blocking switch in neurons through a fat-sensing receptor, not through prostaglandins.
primary_references
[ibu-p20089905] A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. (2010). https://pubmed.ncbi.nlm.nih.gov/20089905/ DOI: 10.1523/jneurosci.5045-09.2010
tissue_or_cell_type
Neurons
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 422–433
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neuron-like PC12 and B104 cells and primary cultured neurons with small interfering RNA knockdown · source_derived_draft · unverified_draft
### ibu-pparg-couples-to-rhoa Ibuprofen activates peroxisome proliferator-activated receptor gamma in neuron-like PC12 and B104 cells, activation with traditional agonists mimics the RhoA-inhibiting properties of ibuprofen and promotes neurite elongation in primary neurons exposed to axonal growth inhibitors, small interfering RNA against the receptor blocks RhoA suppression by those agonists, and selective receptor inhibition prevents the effect of ibuprofen on RhoA activity and neurite growth, supporting an essential role for the receptor in coupling ibuprofen to RhoA inhibition. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The drug reaches a growth-blocking switch in neurons through a fat-sensing receptor, not through prostaglandins. organism: Rat tissue_or_cell_type: Neurons experimental_model: Neuron-like PC12 and B104 cells and primary cultured neurons with small interfering RNA knockdown limitations: The knockdown and the selective antagonist together make the receptor requirement a test rather than a correlation. Cell lines and primary culture rather than an animal. exposure: Ibuprofen with peroxisome proliferator-activated receptor gamma agonists, antagonists and knockdown evidence_span: {"source_cache": "artifacts/ibuprofen-research/20089905.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77e2dbb010dcee44bd66645ec26cb844d7041ea4930f6373ae5dd6b10da37df3", "start_char": 0, "end_char": 1812, "text_sha256": "77e2dbb010dcee44bd66645ec26cb844d7041ea4930f6373ae5dd6b10da37df3"} [ibu-p20089905] A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. (2010). https://pubmed.ncbi.nlm.nih.gov/20089905/ DOI: 10.1523/jneurosci.5045-09.2010
Complete structured claim and evidence
In APPsw transgenic mice, ibuprofen effects were not mediated by alterations in amyloid precursor protein expression or oxidative damage, six months of treatment in transgene-positive females decreased open field behaviour to values similar to transgene-negative mice and reduced caspase activation per plaque, and a shorter three month trial begun at 14 months produced a significant treatment effect on amyloid-beta levels with reductions of both soluble amyloid-beta and amyloid-beta 42 most marked in entorhinal cortex, the magnitude of the effect on soluble amyloid-beta not depending on treatment duration.
Ibuprofen → Amyloid-beta 42, the 42-residue isoform source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/11755007.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85bd65aa6bff20262f11cfa0cd26a25a327aff114898605cea3a0cc05459192b", "start_char": 0, "end_char": 1213, "text_sha256": "85bd65aa6bff20262f11cfa0cd26a25a327aff114898605cea3a0cc05459192b"}
experimental_model
Six month and three month ibuprofen treatment of APPsw Tg2576 transgenic mice with behavioural and biochemical endpoints
exposure
Ibuprofen begun at different ages, with soluble and insoluble amyloid-beta and open field behaviour measured
limitations
An in vivo test with a behavioural endpoint and two treatment durations. A transgenic model of amyloid deposition, which is not Alzheimer’s disease.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Mouse
plain_language
In mice bred to deposit amyloid, the drug lowered the peptide and changed their behaviour back toward normal.
primary_references
[ibu-p11755007] Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. (2001). https://pubmed.ncbi.nlm.nih.gov/11755007/ DOI: 10.1016/s0197-4580(01)00299-8
tissue_or_cell_type
Brain
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 435–446
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six month and three month ibuprofen treatment of APPsw Tg2576 transgenic mice with behavioural and biochemical endpoints · source_derived_draft · unverified_draft
### ibu-in-vivo-and-behavioural In APPsw transgenic mice, ibuprofen effects were not mediated by alterations in amyloid precursor protein expression or oxidative damage, six months of treatment in transgene-positive females decreased open field behaviour to values similar to transgene-negative mice and reduced caspase activation per plaque, and a shorter three month trial begun at 14 months produced a significant treatment effect on amyloid-beta levels with reductions of both soluble amyloid-beta and amyloid-beta 42 most marked in entorhinal cortex, the magnitude of the effect on soluble amyloid-beta not depending on treatment duration. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: In mice bred to deposit amyloid, the drug lowered the peptide and changed their behaviour back toward normal. organism: Mouse tissue_or_cell_type: Brain experimental_model: Six month and three month ibuprofen treatment of APPsw Tg2576 transgenic mice with behavioural and biochemical endpoints limitations: An in vivo test with a behavioural endpoint and two treatment durations. A transgenic model of amyloid deposition, which is not Alzheimer’s disease. exposure: Ibuprofen begun at different ages, with soluble and insoluble amyloid-beta and open field behaviour measured evidence_span: {"source_cache": "artifacts/ibuprofen-research/11755007.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85bd65aa6bff20262f11cfa0cd26a25a327aff114898605cea3a0cc05459192b", "start_char": 0, "end_char": 1213, "text_sha256": "85bd65aa6bff20262f11cfa0cd26a25a327aff114898605cea3a0cc05459192b"} [ibu-p11755007] Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. (2001). https://pubmed.ncbi.nlm.nih.gov/11755007/ DOI: 10.1016/s0197-4580(01)00299-8
Complete structured claim and evidence
The time-dependent reduction in potency of anandamide toward inhibition of cannabinoid agonist binding in rat cerebellar membranes was blocked by ibuprofen but not by acetylsalicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen, a direct assay of anandamide amidase gave a half-maximal inhibitory concentration for ibuprofen of approximately 400 micromolar, and that potency was of the same order as required for inhibition of cyclooxygenase-2 in cell-free systems and as the peak plasma concentrations following a two times 200 milligram dose regimen, so following therapeutic doses the metabolism of anandamide may be affected.
Ibuprofen → Metabolism of anandamide by amidohydrolase source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay
exposure
Ibuprofen compared against acetylsalicylic acid, sulindac, acetaminophen, ketoprofen and naproxen
limitations
The comparator set is what distinguishes this from a class effect: five other drugs failed. The concentration required is high, and the authors relate it to peak plasma levels rather than measuring them.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat
plain_language
Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal.
primary_references
[ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x
tissue_or_cell_type
Cerebellar membranes
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 448–459
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay · source_derived_draft · unverified_draft
### ibu-blocks-anandamide-breakdown The time-dependent reduction in potency of anandamide toward inhibition of cannabinoid agonist binding in rat cerebellar membranes was blocked by ibuprofen but not by acetylsalicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen, a direct assay of anandamide amidase gave a half-maximal inhibitory concentration for ibuprofen of approximately 400 micromolar, and that potency was of the same order as required for inhibition of cyclooxygenase-2 in cell-free systems and as the peak plasma concentrations following a two times 200 milligram dose regimen, so following therapeutic doses the metabolism of anandamide may be affected. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal. organism: Rat tissue_or_cell_type: Cerebellar membranes experimental_model: Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay limitations: The comparator set is what distinguishes this from a class effect: five other drugs failed. The concentration required is high, and the authors relate it to peak plasma levels rather than measuring them. exposure: Ibuprofen compared against acetylsalicylic acid, sulindac, acetaminophen, ketoprofen and naproxen evidence_span: {"source_cache": "artifacts/ibuprofen-research/9060042.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543", "start_char": 0, "end_char": 1394, "text_sha256": "2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543"} [ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x
Complete structured claim and evidence
In 10 patients with chronic glomerular disease randomly assigned to one week of ibuprofen, urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 excretion fell by 80%, serum creatinine rose by 40% and creatinine and para-aminohippurate clearances fell by 28% and 35% respectively, with the reduction in both clearances inversely related to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2, while no functional changes were detected in five healthy women despite a similar suppression of renal prostacyclin synthesis, and one week of sulindac did not affect renal prostacyclin synthesis or renal function despite marked inhibition of extrarenal cyclooxygenase.
Ibuprofen → Glomerular filtration rate measured by creatinine clearance source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/6361565.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b", "start_char": 0, "end_char": 1550, "text_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b"}
experimental_model
Randomised one week treatment in 20 women with chronic glomerular disease and 5 healthy women
exposure
Ibuprofen for one week, against sulindac in a parallel group
limitations
The healthy comparison group is what makes this decisive: the same suppression of renal prostacyclin produced no functional change in them. Twenty patients, one week.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
The same drop in kidney prostaglandins does nothing to a healthy kidney and takes a third of the function from a diseased one.
primary_references
[ibu-p6361565] Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. (1984). https://pubmed.ncbi.nlm.nih.gov/6361565/ DOI: 10.1056/nejm198402023100502
tissue_or_cell_type
Kidney
trigger_kind
biomarker_context Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 461–472
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised one week treatment in 20 women with chronic glomerular disease and 5 healthy women · source_derived_draft · unverified_draft
### ibu-kidney-depends-on-what-is-blocked In 10 patients with chronic glomerular disease randomly assigned to one week of ibuprofen, urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 excretion fell by 80%, serum creatinine rose by 40% and creatinine and para-aminohippurate clearances fell by 28% and 35% respectively, with the reduction in both clearances inversely related to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2, while no functional changes were detected in five healthy women despite a similar suppression of renal prostacyclin synthesis, and one week of sulindac did not affect renal prostacyclin synthesis or renal function despite marked inhibition of extrarenal cyclooxygenase. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The same drop in kidney prostaglandins does nothing to a healthy kidney and takes a third of the function from a diseased one. organism: Human tissue_or_cell_type: Kidney experimental_model: Randomised one week treatment in 20 women with chronic glomerular disease and 5 healthy women limitations: The healthy comparison group is what makes this decisive: the same suppression of renal prostacyclin produced no functional change in them. Twenty patients, one week. exposure: Ibuprofen for one week, against sulindac in a parallel group evidence_span: {"source_cache": "artifacts/ibuprofen-research/6361565.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b", "start_char": 0, "end_char": 1550, "text_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b"} [ibu-p6361565] Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. (1984). https://pubmed.ncbi.nlm.nih.gov/6361565/ DOI: 10.1056/nejm198402023100502
Complete structured claim and evidence
Vasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischaemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II, vasopressin or norepinephrine, indomethacin potentiates the renal actions of angiotensin II in vivo particularly the reduction of renal blood flow and filtration rate, and in dogs after chronic bile duct ligation cyclooxygenase inhibition by indomethacin, ibuprofen, naproxen or sulindac sulfide produced a comparable 50% decrease in both renal blood flow and filtration rate.
The vasodilatory prostaglandin reserve that supports renal blood flow under stress → Glomerular filtration rate measured by creatinine clearance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/6595999.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2", "start_char": 0, "end_char": 2422, "text_sha256": "cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2"}
experimental_model
Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data
exposure
Cyclooxygenase inhibition against a background of raised vasoconstrictor tone
limitations
A review assembling several models rather than one experiment. It states the conditional nature of the renal prostaglandin role, which is the point recorded here.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Rat, dog and human
plain_language
These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not.
primary_references
[ibu-p6595999] Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. (1984). https://pubmed.ncbi.nlm.nih.gov/6595999/ DOI: 10.1007/978-3-642-69132-4_56
tissue_or_cell_type
Renal cortex and glomeruli
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 474–485
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data · source_derived_draft · unverified_draft
### ibu-a-reserve-not-a-baseline Vasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischaemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II, vasopressin or norepinephrine, indomethacin potentiates the renal actions of angiotensin II in vivo particularly the reduction of renal blood flow and filtration rate, and in dogs after chronic bile duct ligation cyclooxygenase inhibition by indomethacin, ibuprofen, naproxen or sulindac sulfide produced a comparable 50% decrease in both renal blood flow and filtration rate. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not. organism: Rat, dog and human tissue_or_cell_type: Renal cortex and glomeruli experimental_model: Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data limitations: A review assembling several models rather than one experiment. It states the conditional nature of the renal prostaglandin role, which is the point recorded here. exposure: Cyclooxygenase inhibition against a background of raised vasoconstrictor tone evidence_span: {"source_cache": "artifacts/ibuprofen-research/6595999.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2", "start_char": 0, "end_char": 2422, "text_sha256": "cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2"} [ibu-p6595999] Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. (1984). https://pubmed.ncbi.nlm.nih.gov/6595999/ DOI: 10.1007/978-3-642-69132-4_56
Complete structured claim and evidence
Indomethacin produced severe acute mesenteric vasoconstriction by intravenous infusion and by intra-arterial injection with rapid tachyphylaxis, whereas ibuprofen did not alter mesenteric blood flow even when a large 50 milligram bolus was rapidly injected, and the indomethacin response was not modified when prostaglandin synthesis was inhibited nor significantly mediated by alpha adrenergic agents or serotonin, while both drugs raised aortic pressure and reduced renal blood flow by small but significant amounts.
Ibuprofen → Mesenteric vascular resistance source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Regional vascular resistance measurement in pentobarbital-anaesthetised dogs
exposure
Indomethacin and ibuprofen given intravenously and intra-arterially, including a 50 milligram intravenous bolus
limitations
A direct head-to-head between two drugs of the same class in the same animals, with a negative result for ibuprofen. Anaesthetised dogs.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Dog
plain_language
One drug of this class strangles the gut circulation and the other does not, and it is not a prostaglandin effect.
primary_references
[ibu-p7299691] Differential effects of ibuprofen and indomethacin in the regional circulation of the dog. (1981). https://pubmed.ncbi.nlm.nih.gov/7299691/ DOI: 10.1016/s0022-3565(25)32861-2
tissue_or_cell_type
Mesenteric and renal circulations
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 487–498
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional vascular resistance measurement in pentobarbital-anaesthetised dogs · source_derived_draft · unverified_draft
### ibu-not-a-class-effect Indomethacin produced severe acute mesenteric vasoconstriction by intravenous infusion and by intra-arterial injection with rapid tachyphylaxis, whereas ibuprofen did not alter mesenteric blood flow even when a large 50 milligram bolus was rapidly injected, and the indomethacin response was not modified when prostaglandin synthesis was inhibited nor significantly mediated by alpha adrenergic agents or serotonin, while both drugs raised aortic pressure and reduced renal blood flow by small but significant amounts. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: One drug of this class strangles the gut circulation and the other does not, and it is not a prostaglandin effect. organism: Dog tissue_or_cell_type: Mesenteric and renal circulations experimental_model: Regional vascular resistance measurement in pentobarbital-anaesthetised dogs limitations: A direct head-to-head between two drugs of the same class in the same animals, with a negative result for ibuprofen. Anaesthetised dogs. exposure: Indomethacin and ibuprofen given intravenously and intra-arterially, including a 50 milligram intravenous bolus evidence_span: {"source_cache": "artifacts/ibuprofen-research/7299691.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "217a7f084ce5301b9b357bed0af13552ba7114c56c9d2692852bd4581450a02d", "start_char": 0, "end_char": 1542, "text_sha256": "217a7f084ce5301b9b357bed0af13552ba7114c56c9d2692852bd4581450a02d"} [ibu-p7299691] Differential effects of ibuprofen and indomethacin in the regional circulation of the dog. (1981). https://pubmed.ncbi.nlm.nih.gov/7299691/ DOI: 10.1016/s0022-3565(25)32861-2
Complete structured claim and evidence
A range of non-steroidal anti-inflammatory agents including acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin inhibit gastric bicarbonate transport in isolated mucosal preparations, effects which can be antagonised by exogenous prostaglandins of the E series, and while the secreted mucus gel overlying the epithelial surface is not affected in the short term a number of these agents inhibit glycoprotein biosynthesis by the epithelial cells, so that loss of this protective coat could be anticipated during chronic exposure as erosion by luminal shear and proteolysis would not be compensated by continued secretion.
Ibuprofen → Gastroduodenal bicarbonate transport source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/3303291.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7", "start_char": 0, "end_char": 1757, "text_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7"}
experimental_model
Review of gastroduodenal defence with isolated mucosal preparations
exposure
Acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin on bicarbonate transport and glycoprotein synthesis
limitations
A review of mechanisms rather than an outcome study. The claim that E-series prostaglandins reverse the effect is what ties it to cyclooxygenase.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human and animal
plain_language
The stomach’s own defences are built by prostaglandins, so blocking them removes the coat rather than adding an acid.
primary_references
[ibu-p3303291] Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents. (1987). https://pubmed.ncbi.nlm.nih.gov/3303291/ DOI: 10.3109/00365528709090947
tissue_or_cell_type
Gastric and duodenal mucosa
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 500–511
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of gastroduodenal defence with isolated mucosal preparations · source_derived_draft · unverified_draft
### ibu-bicarbonate-and-mucus A range of non-steroidal anti-inflammatory agents including acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin inhibit gastric bicarbonate transport in isolated mucosal preparations, effects which can be antagonised by exogenous prostaglandins of the E series, and while the secreted mucus gel overlying the epithelial surface is not affected in the short term a number of these agents inhibit glycoprotein biosynthesis by the epithelial cells, so that loss of this protective coat could be anticipated during chronic exposure as erosion by luminal shear and proteolysis would not be compensated by continued secretion. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The stomach’s own defences are built by prostaglandins, so blocking them removes the coat rather than adding an acid. organism: Human and animal tissue_or_cell_type: Gastric and duodenal mucosa experimental_model: Review of gastroduodenal defence with isolated mucosal preparations limitations: A review of mechanisms rather than an outcome study. The claim that E-series prostaglandins reverse the effect is what ties it to cyclooxygenase. exposure: Acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin on bicarbonate transport and glycoprotein synthesis evidence_span: {"source_cache": "artifacts/ibuprofen-research/3303291.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7", "start_char": 0, "end_char": 1757, "text_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7"} [ibu-p3303291] Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents. (1987). https://pubmed.ncbi.nlm.nih.gov/3303291/ DOI: 10.3109/00365528709090947
Complete structured claim and evidence
At low oxygen tension ibuprofen produced a dose-dependent contraction of isolated lamb ductus arteriosus strips at all gestational ages and enhanced the potassium-induced contraction of the immature ductus, both effects being relatively greater in the 103 to 107 day group where ibuprofen also potentiated the oxygen-induced contraction, confirming that a prostaglandin is involved in ductus patency and indicating that the prostaglandin-relaxing mechanism becomes functional at an early stage of gestation and reaches maximal activity before term.
Ibuprofen → Patency of the ductus arteriosus source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/497895.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9d0874e6d05ee46097aeebdc1f0b9024541aa1305a648d6b783c329108a0bf0f", "start_char": 0, "end_char": 1229, "text_sha256": "9d0874e6d05ee46097aeebdc1f0b9024541aa1305a648d6b783c329108a0bf0f"}
experimental_model
Circular strips of lamb ductus arteriosus from 90 to 144 days gestation studied in vitro at low and high oxygen tension
exposure
Ibuprofen applied at low oxygen tension across gestational ages, with potassium and oxygen contractions
limitations
An isolated tissue study across a developmental range, which is what reveals that the prostaglandin brake matures before term. In vitro strips rather than a treated infant.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Lamb
plain_language
Blocking prostaglandins closes the vessel that has to close at birth, which is why the drug is used for that on purpose.
primary_references
[ibu-p497895] Age-dependent changes in the response of the lamb ductus arteriosus to oxygen and ibuprofen. (1979). https://pubmed.ncbi.nlm.nih.gov/497895/ DOI: 10.1139/y79-126
tissue_or_cell_type
Ductus arteriosus
trigger_kind
biomarker_context Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 513–524
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Circular strips of lamb ductus arteriosus from 90 to 144 days gestation studied in vitro at low and high oxygen tension · source_derived_draft · unverified_draft
### ibu-closes-the-ductus At low oxygen tension ibuprofen produced a dose-dependent contraction of isolated lamb ductus arteriosus strips at all gestational ages and enhanced the potassium-induced contraction of the immature ductus, both effects being relatively greater in the 103 to 107 day group where ibuprofen also potentiated the oxygen-induced contraction, confirming that a prostaglandin is involved in ductus patency and indicating that the prostaglandin-relaxing mechanism becomes functional at an early stage of gestation and reaches maximal activity before term. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Blocking prostaglandins closes the vessel that has to close at birth, which is why the drug is used for that on purpose. organism: Lamb tissue_or_cell_type: Ductus arteriosus experimental_model: Circular strips of lamb ductus arteriosus from 90 to 144 days gestation studied in vitro at low and high oxygen tension limitations: An isolated tissue study across a developmental range, which is what reveals that the prostaglandin brake matures before term. In vitro strips rather than a treated infant. exposure: Ibuprofen applied at low oxygen tension across gestational ages, with potassium and oxygen contractions evidence_span: {"source_cache": "artifacts/ibuprofen-research/497895.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9d0874e6d05ee46097aeebdc1f0b9024541aa1305a648d6b783c329108a0bf0f", "start_char": 0, "end_char": 1229, "text_sha256": "9d0874e6d05ee46097aeebdc1f0b9024541aa1305a648d6b783c329108a0bf0f"} [ibu-p497895] Age-dependent changes in the response of the lamb ductus arteriosus to oxygen and ibuprofen. (1979). https://pubmed.ncbi.nlm.nih.gov/497895/ DOI: 10.1139/y79-126
Complete structured claim and evidence
Ibuprofen but not celecoxib significantly inhibited thromboxane-dependent platelet aggregation induced ex vivo by arachidonic acid, 83% against 11.9%, and reduced serum thromboxane B2 by 95% and urinary 11-dehydro thromboxane B2 by 70%, while both ibuprofen and celecoxib suppressed an index of cyclooxygenase-2 activity to a comparable degree and both suppressed urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha, data suggesting that cyclooxygenase-2 is a major source of systemic prostacyclin biosynthesis in healthy humans.
Ibuprofen → Systemic prostacyclin biosynthesis measured as urinary 2,3-dinor-6-keto-prostaglandin F1 alpha source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ibuprofen-research/9874808.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4", "start_char": 0, "end_char": 1789, "text_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4"}
experimental_model
Volunteers given celecoxib at three doses or ibuprofen, with platelet, serum and urinary indices
exposure
800 milligrams ibuprofen against 100, 400 or 800 milligrams celecoxib
limitations
Measures both isoform-specific indices in the same people, which is what allows the prostacyclin source to be assigned. Acute dosing in healthy volunteers.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
The enzyme these drugs are meant to spare the stomach by blocking is the one that makes the body’s main anticlotting prostaglandin.
primary_references
[ibu-p9874808] Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. (1999). https://pubmed.ncbi.nlm.nih.gov/9874808/ DOI: 10.1073/pnas.96.1.272
tissue_or_cell_type
Platelets and whole body
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 526–537
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Volunteers given celecoxib at three doses or ibuprofen, with platelet, serum and urinary indices · source_derived_draft · unverified_draft
### ibu-cox2-makes-the-prostacyclin Ibuprofen but not celecoxib significantly inhibited thromboxane-dependent platelet aggregation induced ex vivo by arachidonic acid, 83% against 11.9%, and reduced serum thromboxane B2 by 95% and urinary 11-dehydro thromboxane B2 by 70%, while both ibuprofen and celecoxib suppressed an index of cyclooxygenase-2 activity to a comparable degree and both suppressed urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha, data suggesting that cyclooxygenase-2 is a major source of systemic prostacyclin biosynthesis in healthy humans. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The enzyme these drugs are meant to spare the stomach by blocking is the one that makes the body’s main anticlotting prostaglandin. organism: Human tissue_or_cell_type: Platelets and whole body experimental_model: Volunteers given celecoxib at three doses or ibuprofen, with platelet, serum and urinary indices limitations: Measures both isoform-specific indices in the same people, which is what allows the prostacyclin source to be assigned. Acute dosing in healthy volunteers. exposure: 800 milligrams ibuprofen against 100, 400 or 800 milligrams celecoxib evidence_span: {"source_cache": "artifacts/ibuprofen-research/9874808.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4", "start_char": 0, "end_char": 1789, "text_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4"} [ibu-p9874808] Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. (1999). https://pubmed.ncbi.nlm.nih.gov/9874808/ DOI: 10.1073/pnas.96.1.272
Complete structured claim and evidence
A 53-year-old aspirin-sensitive asthmatic man with nasal polyps developed an urticarial rash, laboured breathing, laryngeal oedema and chest tightness after a 400 milligram ibuprofen tablet, requiring isoproterenol, subcutaneous epinephrine, intramuscular diphenhydramine and intravenous hydrocortisone; the reaction was not mediated immunologically but resulted from the prostaglandin synthetase inhibitor activity shared by aspirin, ibuprofen and other analgesics, so selection of an analgesic for an aspirin-sensitive patient should be based on that activity.
Ibuprofen → Urticaria, laryngeal oedema and bronchospasm source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/696734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139", "start_char": 0, "end_char": 949, "text_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139"}
experimental_model
Clinical case report of an adverse reaction in an aspirin-sensitive asthmatic
exposure
A single 400 milligram ibuprofen tablet in a 53-year-old aspirin-sensitive asthmatic with nasal polyps
limitations
A single case, but it identifies the basis of the reaction as shared pharmacology rather than immunology, which is what determines whether a substitute drug is safe.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
The reaction is not an allergy to the drug but to what the drug does, so any drug that does the same thing will do it too.
primary_references
[ibu-p696734] Cross-reactivity between aspirin and ibuprofen in an asthmatic--a case report. (1978). https://pubmed.ncbi.nlm.nih.gov/696734/ DOI: 10.1093/ajhp/35.10.1245
tissue_or_cell_type
Airway and skin
trigger_kind
biomarker_context Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 539–550
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical case report of an adverse reaction in an aspirin-sensitive asthmatic · source_derived_draft · unverified_draft
### ibu-cross-reacts-pharmacologically A 53-year-old aspirin-sensitive asthmatic man with nasal polyps developed an urticarial rash, laboured breathing, laryngeal oedema and chest tightness after a 400 milligram ibuprofen tablet, requiring isoproterenol, subcutaneous epinephrine, intramuscular diphenhydramine and intravenous hydrocortisone; the reaction was not mediated immunologically but resulted from the prostaglandin synthetase inhibitor activity shared by aspirin, ibuprofen and other analgesics, so selection of an analgesic for an aspirin-sensitive patient should be based on that activity. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The reaction is not an allergy to the drug but to what the drug does, so any drug that does the same thing will do it too. organism: Human tissue_or_cell_type: Airway and skin experimental_model: Clinical case report of an adverse reaction in an aspirin-sensitive asthmatic limitations: A single case, but it identifies the basis of the reaction as shared pharmacology rather than immunology, which is what determines whether a substitute drug is safe. exposure: A single 400 milligram ibuprofen tablet in a 53-year-old aspirin-sensitive asthmatic with nasal polyps evidence_span: {"source_cache": "artifacts/ibuprofen-research/696734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139", "start_char": 0, "end_char": 949, "text_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139"} [ibu-p696734] Cross-reactivity between aspirin and ibuprofen in an asthmatic--a case report. (1978). https://pubmed.ncbi.nlm.nih.gov/696734/ DOI: 10.1093/ajhp/35.10.1245
Complete structured claim and evidence
A probable case of acute reversible renal failure with hyperkalaemia followed an increase in ibuprofen dose, and across reviewed cases the ability of these drugs to inhibit prostaglandin synthesis may explain the various renal consequences, with possible predisposing factors including the amount of drug consumed, compromised renal blood flow, underlying renal insufficiency, nephrotoxic drug combinations and high urinary prostaglandin excretion; renal failure with these drugs is generally acute and reversible although analgesic nephropathy with papillary necrosis and chronic failure are reported.
Ibuprofen → Serum creatinine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ibuprofen-research/6420135.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "efb8422d9d57d38da8a5cea4e37f5c6e043c527d2a59f8fee8cfe5ffcf29daf7", "start_char": 0, "end_char": 957, "text_sha256": "efb8422d9d57d38da8a5cea4e37f5c6e043c527d2a59f8fee8cfe5ffcf29daf7"}
experimental_model
Case report of acute reversible renal failure with review of non-steroidal anti-inflammatory drug nephrotoxicity
exposure
An increase in ibuprofen dose in a susceptible patient
limitations
A single case with a narrative review. The predisposing factors listed are the authors’ synthesis rather than a measured risk model.
nutrient_topic
Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen
organism
Human
plain_language
The kidney injury usually reverses when the drug stops, and the people at risk are the ones already leaning on prostaglandins.
primary_references
[ibu-p6420135] Reversible renal failure associated with ibuprofen: case report and review of the literature. (1984). https://pubmed.ncbi.nlm.nih.gov/6420135/ DOI: 10.1177/106002808401800103
tissue_or_cell_type
Kidney
trigger_kind
biomarker_context Imported condition classification; unverified.
Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 552–563
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case report of acute reversible renal failure with review of non-steroidal anti-inflammatory drug nephrotoxicity · source_derived_draft · unverified_draft
### ibu-renal-failure-is-reversible A probable case of acute reversible renal failure with hyperkalaemia followed an increase in ibuprofen dose, and across reviewed cases the ability of these drugs to inhibit prostaglandin synthesis may explain the various renal consequences, with possible predisposing factors including the amount of drug consumed, compromised renal blood flow, underlying renal insufficiency, nephrotoxic drug combinations and high urinary prostaglandin excretion; renal failure with these drugs is generally acute and reversible although analgesic nephropathy with papillary necrosis and chronic failure are reported. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The kidney injury usually reverses when the drug stops, and the people at risk are the ones already leaning on prostaglandins. organism: Human tissue_or_cell_type: Kidney experimental_model: Case report of acute reversible renal failure with review of non-steroidal anti-inflammatory drug nephrotoxicity limitations: A single case with a narrative review. The predisposing factors listed are the authors’ synthesis rather than a measured risk model. exposure: An increase in ibuprofen dose in a susceptible patient evidence_span: {"source_cache": "artifacts/ibuprofen-research/6420135.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "efb8422d9d57d38da8a5cea4e37f5c6e043c527d2a59f8fee8cfe5ffcf29daf7", "start_char": 0, "end_char": 957, "text_sha256": "efb8422d9d57d38da8a5cea4e37f5c6e043c527d2a59f8fee8cfe5ffcf29daf7"} [ibu-p6420135] Reversible renal failure associated with ibuprofen: case report and review of the literature. (1984). https://pubmed.ncbi.nlm.nih.gov/6420135/ DOI: 10.1177/106002808401800103
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

When a racemate is treated as a single compound

Condition: biomarker_context · Measuring the enantiomers separately rather than as total drug.

Normal role: Ibuprofen is swallowed as a 50:50 mixture of two enantiomers and is usually measured and prescribed as one substance.

Recorded consequence: About 63% of the R enantiomer is converted to S with no measurable conversion back, the two are bound to plasma protein to different extents, they are hydroxylated by different cytochromes, and each alters the kinetics of the other, so total-drug measurements cannot be interpreted.

Scope: Four healthy men given the racemate and each enantiomer separately

When inflammation itself slows the activation step

Condition: machinery_impairment · Adjuvant-induced arthritis, which is the kind of condition the drug is given for.

Normal role: R-ibuprofen is converted to the active S enantiomer after being activated to its coenzyme A thioester by acyl-CoA synthetase.

Recorded consequence: Acyl-CoA synthetase messenger RNA falls while the epimerase is unchanged, and the chiral inversion rate constant drops to about 64 to 80% of control.

Scope: Freshly isolated rat hepatocytes

When the enzyme that clears the active enantiomer is slow

Condition: machinery_impairment · Carriage of the CYP2C9 isoleucine 359 leucine variant, CYP2C9*3.

Normal role: S-ibuprofen, the cyclooxygenase-inhibiting enantiomer, is hydroxylated and cleared largely by CYP2C9.

Recorded consequence: S-ibuprofen clearance falls from 3.25 to 1.52 litres per hour between *1/*1 and *3/*3 carriers, and both the maximal inhibition of thromboxane B2 formation and the area under the effect-time curve are larger, so the drug effect is greater as well as longer.

Scope: 21 healthy volunteers genotyped across all variant combinations

When the enantiomer called inactive turns out to do something

Condition: biomarker_context · Measuring an endpoint that is not cyclooxygenase.

Normal role: R-ibuprofen inhibits cyclooxygenase-1 thirty-two to ninety-six fold less than S and has long been described as the inactive enantiomer, valued only as a reservoir that inverts to S.

Recorded consequence: R-ibuprofen and R-flurbiprofen reduce amyloid-beta 42 production despite poor cyclooxygenase inhibition, and R-ibuprofen inhibits nuclear factor kappa B only twofold less potently than S; the amyloid-beta 42 reduction is not mediated by that inhibition either.

Scope: Human cultured cells

When the kidney is already leaning on prostaglandins

Condition: biomarker_context · Chronic glomerular disease, or any state in which vasoconstrictor tone is high.

Normal role: Renal prostaglandins contribute little to blood flow in a healthy kidney and the drug can suppress them without consequence.

Recorded consequence: Renal prostacyclin and prostaglandin E2 fall by 80% in patients and in healthy controls alike, but only in the patients does glomerular filtration fall 28%, renal plasma flow 35% and serum creatinine rise 40%, with the fall in clearance inversely related to the basal prostacyclin output.

Scope: 20 women with chronic glomerular disease and 5 healthy women, one week

When blocking prostaglandins is the point

Condition: biomarker_context · A premature infant in whom the ductus arteriosus has failed to close.

Normal role: Prostaglandins hold the ductus arteriosus open before birth, and in most tissues blocking prostaglandin synthesis is an unwanted effect of this drug.

Recorded consequence: The same cyclooxygenase inhibition that is a side effect elsewhere contracts the ductus in a dose-dependent way at every gestational age tested, which is the basis of its use to close the vessel.

Scope: Isolated lamb ductus strips from 90 to 144 days gestation

When the patient already reacts to aspirin

Condition: biomarker_context · Established aspirin-sensitive asthma with nasal polyps.

Normal role: Ibuprofen and aspirin are chemically unrelated, so a reaction to one need not predict a reaction to the other.

Recorded consequence: A single 400 milligram tablet produced urticaria, laryngeal oedema and bronchospasm, through the cyclooxygenase-inhibiting activity the two drugs share rather than through an immune mechanism, so cross-reactivity follows potency at that enzyme and not chemical similarity.

Scope: A single reported case

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

By what route does ibuprofen lower amyloid-beta 42?Three mechanisms are proposed in this collection and they are not the same. The original report attributed the effect to a subtle alteration of gamma-secretase activity, shifting production from amyloid-beta 42 toward amyloid-beta 38 without perturbing Notch cleavage, and showed it was not shared by all cyclooxygenase inhibitors. A study of the enantiomers found that R-ibuprofen, which barely inhibits cyclooxygenase, lowers the peptide, and explicitly excluded nuclear factor kappa B inhibition as the mediator even though the R enantiomers do inhibit that factor. A third route runs through peroxisome proliferator-activated receptor gamma to RhoA, with receptor knockdown and selective antagonism both abolishing the effect on RhoA and neurite growth. A cell-free assay of a related drug shows direct noncompetitive action on gamma-secretase itself. These are not mutually exclusive and the records do not weigh them against each other. What is agreed is that the route is not cyclooxygenase inhibition.Read the recorded disagreement
Is R-ibuprofen the inactive enantiomer?It is routinely called that, and at cyclooxygenase the description is accurate: S is 32-, 41- and 96-fold more potent for inhibition of cyclooxygenase-1, platelet aggregation and serotonin release, and a 1997 cloning paper states plainly that the R enantiomer is inactive in terms of cyclooxygenase inhibition. On three other measures it is not inactive at all. It inhibits nuclear factor kappa B with a half-maximal concentration of 121.8 micromolar against 61.7 for S, a twofold gap rather than a thirtyfold one. It lowers amyloid-beta 42 production despite that poor cyclooxygenase activity, and by a route that is not nuclear factor kappa B. And it is the only enantiomer that acyl-CoA synthetase will activate, which is what drives the inversion to S and what gets it built into triacylglycerol. At cyclooxygenase-2 the two enantiomers are indistinguishable. The word inactive is a statement about one target that has been generalised to the molecule, and this chapter keeps the two enantiomers as separate entities so that the generalisation cannot be made silently.Read the recorded disagreement
Is ibuprofen selective between the two cyclooxygenases?Measured on purified and recombinant enzyme, S-ibuprofen was 27-fold more potent against cyclooxygenase-1 than against cyclooxygenase-2, which would make the drug appreciably cyclooxygenase-1 selective, and the two enantiomers differed 32-fold at cyclooxygenase-1 while showing no selectivity at all at cyclooxygenase-2. Measured in human whole blood at therapeutically relevant concentrations, standard drugs of this class inhibited both isoforms to an equal degree and only meloxicam showed selectivity. A third record shows why the two need not agree: potencies and selectivities determined in intact cells depend on substrate concentration and differ from those obtained in cell-free microsomal or purified preparations, and protein binding, which is high and stereoselective for this drug, is absent from purified systems. The ratio is therefore a property of the assay as much as of the drug, and no single selectivity figure for ibuprofen is supported here.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Whether R-ibuprofen contributes anything to the effect of a tablet beyond serving as a reservoir for S.It inhibits nuclear factor kappa B only twofold less potently than S, it lowers amyloid-beta 42 where S has not been shown to, and it is the only enantiomer activated to a coenzyme A thioester. No record here measures what fraction of the clinical effect of the racemate it accounts for.
Whether being built into body triglycerides has any consequence.The stereospecific incorporation of R-2-arylpropionic acids into triacylglycerol occurs at clinically relevant unbound concentrations, and the enzyme responsible for the inversion is homologous to carnitine dehydratases and may have a role in lipid metabolism. No record here follows what happens to those hybrid lipids or whether they perturb anything.
What selectivity ratio between the two cyclooxygenases ibuprofen actually has in a person.Purified enzyme gives 27-fold selectivity for cyclooxygenase-1, human whole blood gives none at therapeutic concentrations, and intact-cell potencies depend on substrate concentration and differ from cell-free values. Protein binding, which is high and differs between the enantiomers, is absent from purified systems.
Whether inhibition of anandamide breakdown occurs at doses people take.The half-maximal inhibitory concentration is around 400 micromolar, which the authors relate to peak plasma concentrations after a 200 milligram twice-daily regimen and to the concentration needed for cyclooxygenase-2 inhibition in cell-free systems, but no record here measures anandamide or its amidase in a dosed person.
Whether the chiral inversion step is slowed in the patients who actually take the drug.Adjuvant arthritis in rats lowered acyl-CoA synthetase messenger RNA and slowed inversion in isolated hepatocytes to 64 to 80% of control, but adding serum abolished the difference and no record here measures inversion in people with inflammatory disease.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

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