Flurbiprofen

Where it participates (unsigned role)

1. 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

2. 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

3. No meaningful overall flurbiprofen pharmacokinetic change was found.

   Curcuminoid-piperine preparation, study-specific → Human flurbiprofen plasma exposure source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/curcumin-research/22725836.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127", "start_char": 0, "end_char": 1977, "text_sha256": "255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127"}

   experimental_model

   Randomized six-way crossover in eight healthy volunteers

   exposure

   4 g curcuminoids plus 24 mg piperine, four doses over two days before each probe drug

   limitations

   Short regimen and small sample. A null result for these probes does not establish no interactions with all medicines or preparations.

   nutrient_topic

   Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin

   organism

   Homo sapiens

   plain_language

   The CYP2C9 probe also had a null overall result.

   primary_references

   [curcumin-p22725836] Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/22725836/ DOI: 10.1111/j.1365-2125.2012.04364.x

   tissue_or_cell_type

   Drug pharmacokinetics

   Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 931–942

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized six-way crossover in eight healthy volunteers · source_derived_draft · unverified_draft

   ### curcumin-flurbiprofen-null No meaningful overall flurbiprofen pharmacokinetic change was found. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CYP2C9 probe also had a null overall result. organism: Homo sapiens tissue_or_cell_type: Drug pharmacokinetics experimental_model: Randomized six-way crossover in eight healthy volunteers limitations: Short regimen and small sample. A null result for these probes does not establish no interactions with all medicines or preparations. exposure: 4 g curcuminoids plus 24 mg piperine, four doses over two days before each probe drug evidence_span: {"source_cache": "artifacts/curcumin-research/22725836.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127", "start_char": 0, "end_char": 1977, "text_sha256": "255db8a54957c442fe6fca1d21aafe393e3a5506bec7330b49e1bb6f85d86127"} [curcumin-p22725836] Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/22725836/ DOI: 10.1111/j.1365-2125.2012.04364.x

   Complete structured claim and evidence