Component

Reversible, competitive inhibition of cyclooxygenase

Reversible, competitive inhibition of cyclooxygenase. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

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 acts on it

  1. 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

Where it participates (unsigned role)

  1. 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

  2. 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

In the sources

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