PTGS2 prostaglandin-endoperoxide synthase 2
ENSG00000073756 · protein coding · Open Targets profile
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:17519235, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins respectively, though arachidonate (AA, C20:4(n-6)) remains the preferred substrate (PubMed:11939906, PubMed:17519235, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophospholipids to prostanoid lysophospholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D- series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S- RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13- series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)- octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)- HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity) (PubMed:7642610). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R- lipoxin A4 that regulates phagocytic microglia (By similarity). {ECO:0000250|UniProtKB:P79208, ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:11939906, ECO:0000269|PubMed:12391014, ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:17519235, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:22068350, ECO:0000269|PubMed:22942274, ECO:0000269|PubMed:26236990, ECO:0000269|PubMed:26282205, ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7592599, ECO:0000269|PubMed:7642610, ECO:0000269|PubMed:7947975, ECO:0000269|PubMed:9048568, ECO:0000269|PubMed:9261177, ECO:0000303|PubMed:19540099}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.21950000524520874 (upper bound 0.3431600034236908). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 15 registry trials, updated in the last three years, of the most advanced drugs against PTGS2 (nabumetone, olsalazine, meclofenamate, fenoprofen, fenoprofen calcium, naproxcinod, esflurbiprofen, etodolac, carprofen, diflunisal, tolmetin, meclofenamic acid), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Kenichi NishiyamaTeikoku Seiyaku Co., Ltd. · 2 of 5 trials Phase 2+
- Anna BlecherThe Chaim Sheba Medical Center (Tel Hashomer) · 1 of 1 trials Phase 2+
- Mathew MaurerColumbia University · 1 of 1 trials Phase 2+
- Nadav MichaanTel Aviv Sourasky Medical Center (Ichilov Hospital) · 1 of 1 trials Phase 2+
- Shamgar Ben-EliyahuTel Aviv University · 1 of 1 trials Phase 2+
- Adrienne BoireMemorial Sloan Kettering Cance Center · 0 of 1 trials Phase 2+
- Kara Long RocheMemorial Sloan Kettering Cancer Center · 0 of 1 trials Phase 2+
- Massimiliano GilliAzienda Ospedaliera Perugia · 0 of 1 trials Phase 2+
- Pier Paolo PeruzziBrigham and Women's Hospital · 0 of 1 trials Phase 2+
- Ramazan Yılmaz Associate Professor Dr.Konya Beyhekim Training and Research Hospital · 0 of 1 trials Phase 2+
Registry trials of nabumetone, olsalazine, meclofenamate, fenoprofen, fenoprofen calcium, naproxcinod, esflurbiprofen, etodolac, carprofen, diflunisal, tolmetin, meclofenamic acid updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 14 of 14 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
7 trials of drugs against PTGS2 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of nabumetone, olsalazine, meclofenamate, fenoprofen, fenoprofen calcium, naproxcinod, esflurbiprofen, etodolac, carprofen, diflunisal, tolmetin, meclofenamic acid, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 7 most recent of 7.
- terminated · 2026-09-09 · Apsen Farmaceutica S.A. · Etodolac“recruitment difficulty”
- terminated · 2021-10-19 · Teikoku Seiyaku Co., Ltd. · Esflurbiprofen Hydrogel Patch“Due to lack of patients number”
- terminated · 2018-04-26 · Vicus Therapeutics · matched by the registry's drug synonyms“Low patient recruitment”
- terminated · 2017-10-27 · University of British Columbia · Diflunisal“Insufficient enrollment.”
- terminated · 2014-05-12 · Cephalon · SDX-101 (R-Etodolac)No reason given
- terminated · 2013-01-28 · Stanford University · matched by the registry's drug synonyms“Extreme toxicity”
- terminated · 2012-06-11 · Cephalon · R-etodolac + chlorambucilNo reason given
Paediatric incentives and obligations for PTGS2's drugs
For nabumetone, olsalazine, meclofenamate, fenoprofen, fenoprofen calcium, naproxcinod, esflurbiprofen, etodolac, carprofen, diflunisal, tolmetin, meclofenamic acid: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · PTGS2 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-003490-PIP01-23 (diflunisal, Treatment of transthyretin amyloidosis (ATTR)): W: decision granting a waiver in all age groups for all conditions or indications, 29 Dec 2023; EMEA-000104-PIP01-07 (naproxcinod, Primary osteoarthritis): W: decision granting a waiver in all age groups for all conditions or indications, 31 Mar 2008Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/22/2640 withdrawn 21 Jun 2022: Treatment of ATTR amyloidosis; EU/3/13/1194 withdrawn 7 Oct 2013: Treatment of Duchenne muscular dystrophyRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Attrogy: authorised since 17 Jul 2025; Beprana: application withdrawnRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of nabumetone, olsalazine, meclofenamate, fenoprofen, fenoprofen calcium, naproxcinod, esflurbiprofen, etodolac, carprofen, diflunisal, tolmetin, meclofenamic acidRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 3 interventional studies of nabumetone, olsalazine, meclofenamate, fenoprofen, fenoprofen calcium, naproxcinod, esflurbiprofen, etodolac, carprofen, diflunisal, tolmetin, meclofenamic acid include patients under 18; 0 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 79 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.