The free carboxylate group of a 2-arylpropionic acid inhibitor: molecular mechanisms & dependencies

How nutrients influence it

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Human evidence only

How nutrients reach it in more than one step

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What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

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
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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

What acts on it

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

The events it takes part in

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Situations it appears in

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In the sources

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Open hypotheses

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This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

The free carboxylate group of a 2-arylpropionic acid inhibitor