R(-)-ibuprofen

evidence_span

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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

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

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

availability_state

biomarker_context Imported condition classification; unverified.

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"}

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

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

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

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

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

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

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

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

evidence_span

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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

evidence_span

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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

evidence_span

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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

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