PTGS1

Summary

PTGS1 (prostaglandin-endoperoxide synthase 1, HGNC:9604) is a protein-coding gene on chromosome 9q33.2, encoding Prostaglandin G/H synthase 1 (P23219). Dual cyclooxygenase and peroxidase that plays an important role 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.

This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5742 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet-type bleeding disorder 12 (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 272 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9604
Approved symbol	PTGS1
Name	prostaglandin-endoperoxide synthase 1
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	COX1, PGHS-1, PTGHS
Ensembl gene	ENSG00000095303
Ensembl biotype	protein_coding
OMIM	176805
Entrez	5742

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000223423, ENST00000362012, ENST00000373698, ENST00000426608, ENST00000540753, ENST00000619306, ENST00000643576, ENST00000643810, ENST00000645132, ENST00000647067, ENST00000863389, ENST00000863390, ENST00000863391, ENST00000863392, ENST00000863393

RefSeq mRNA: 7 — MANE Select: NM_000962 NM_000962, NM_001271164, NM_001271165, NM_001271166, NM_001271367, NM_001271368, NM_080591

CCDS: CCDS59520, CCDS59521, CCDS6842, CCDS6843, CCDS75895

Canonical transcript exons

ENST00000362012 — 11 exons

Exon	Start	End
ENSE00001167228	122392189	122395703
ENSE00001608834	122386446	122386732
ENSE00001632249	122390198	122390345
ENSE00001707197	122381664	122381747
ENSE00001732837	122378775	122378918
ENSE00001745009	122381371	122381552
ENSE00001786801	122383509	122383755
ENSE00003462792	122378433	122378573
ENSE00003536647	122377899	122378015
ENSE00003574302	122371186	122371272
ENSE00003825198	122371024	122371091

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.8773 / max 2202.2525, expressed in 1309 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98408	24.5827	1143
98407	16.8946	1132
98410	1.0956	381
98406	1.0129	318
98409	0.2915	106

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.26	gold quality
germinal epithelium of ovary	UBERON:0001304	98.19	gold quality
monocyte	CL:0000576	97.12	gold quality
upper arm skin	UBERON:0004263	96.93	gold quality
mononuclear cell	CL:0000842	96.82	gold quality
leukocyte	CL:0000738	96.37	gold quality
upper leg skin	UBERON:0004262	96.23	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.80	gold quality
parietal pleura	UBERON:0002400	95.72	gold quality
tendon of biceps brachii	UBERON:0008188	95.10	gold quality
lower esophagus	UBERON:0013473	94.85	gold quality
tongue squamous epithelium	UBERON:0006919	94.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.83	gold quality
skin of leg	UBERON:0001511	94.76	gold quality
esophagus squamous epithelium	UBERON:0006920	94.64	gold quality
epithelium of esophagus	UBERON:0001976	94.24	gold quality
zone of skin	UBERON:0000014	93.85	gold quality
skin of abdomen	UBERON:0001416	93.80	gold quality
urinary bladder	UBERON:0001255	93.24	gold quality
nipple	UBERON:0002030	93.24	gold quality
sigmoid colon	UBERON:0001159	92.81	gold quality
esophagus	UBERON:0001043	92.71	gold quality
skin of hip	UBERON:0001554	92.56	gold quality
cervix squamous epithelium	UBERON:0006922	92.55	gold quality
lower esophagus mucosa	UBERON:0035834	92.46	gold quality
mucosa of urinary bladder	UBERON:0001259	92.37	gold quality
pleura	UBERON:0000977	92.06	gold quality
mucosa of stomach	UBERON:0001199	91.57	gold quality
squamous epithelium	UBERON:0006914	91.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.44	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	32.92
E-HCAD-4	yes	29.98
E-CURD-122	yes	23.77
E-HCAD-6	yes	19.37
E-HCAD-10	yes	16.97
E-MTAB-9067	yes	12.06
E-MTAB-8410	yes	9.35
E-GEOD-135922	yes	6.97
E-MTAB-9801	yes	5.92
E-HCAD-1	yes	5.30
E-MTAB-6386	no	278.81
E-MTAB-5061	no	3.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, E2F1, E2F6, ESR1, ESR2, KLF10, KMT2D, NFKB1, NR3C1, PAX3, RELA, SP3

miRNA regulators (miRDB)

107 targeting PTGS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3180-5P	99.82	69.12	2422

Literature-anchored findings (GeneRIF, showing 40)

• Cyclooxygenase-1 is up-regulated in cervical carcinomas: autocrine/paracrine regulation of cyclooxygenase-2, prostaglandin e receptors, and angiogenic factors by cyclooxygenase-1. (PMID:11809691)
• COX-1 is an inducible gene in glial-derived cells including immortalized cells, and appears to be transcriptionally regulated by a unique mechanism associated with histone acetylation (PMID:11877441)
• the effects of several paracrine and/or autocrine signaling pathways in the regulation of expression of aromatase, COX-1, and COX-2 in breast cells has identified complex relationships (PMID:11897504)
• greater expression seen in squamous cell carcinoma rather than adenocarcinoma of lung; no correlation seen between increased expression and major clinicopathologic features (PMID:11920472)
• COX-1 is predominantly present in the thymic cortex, both in the stroma and in developing thymocytes. (PMID:11981837)
• cyclooxygenase gene expression in human preimplantation embryos. (PMID:12050227)
• sequence determination (GenBank deposit), DNA mutational analysis,and genetic linkage analysis; exclusion by genetic linkage analysis as a second modifier gene in familial thrombosis (PMID:12192304)
• Data indicate that both COX-1 and COX-2 contribute to endothelial prostanoid synthesis in the neonatal human brain under basal conditions and in response to proinflammatory cytokine IL-1 beta. (PMID:12193665)
• Human fallopian tubes express prostacyclin (PGI) synthase and cyclooxygenases and synthesize abundant PGI (PMID:12213900)
• Data show that the prostaglandin endoperoxide H synthase-1 (PGHS-1) gene is regulated at the translational level. (PMID:12237309)
• cloning, structure and expression of the COX-3 isozyme (PMID:12242329)
• Results indicate that the cyclooxygenase-2 rather than the cyclooxygenase-1 gene is transcribed consistently in cultivated human iridial melanocytes of both blue and hazel eyes. (PMID:12519124)
• Participants heterozygous for the A842G/C50T haplotype showed significantly greater inhibition of prostaglandin H formation by acetylsalicylic acid compared with common allele homozygotes. (PMID:12545150)
• cyclooxygenase 1 and cyclooxygenase 2 enzyme immunoreactivity is present only in the neoplastic C-cells of medullary carcinoma (PMID:12665651)
• specific co-localization of cPLA2-alpha with cyclooxygenase-1 but not cyclooxygenase-2 was evident at the Golgi apparatus. (PMID:12711701)
• In this study have identified a similar COX-1 splice variant (COX-1SV) in iris and blood tissues with comparable COX-1/COX-1SV expression ratios. (PMID:12711844)
• COX-1 and COX-2 protein expression levels were determined in sets of tumor and normal colon tissue (PMID:12720297)
• In human microvasculature, COX-1 and not COX-2 seems to be the source of prostacyclin. (PMID:12730088)
• mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE2 involved in both tissue homeostasis and disease. (PMID:12835322)
• Retinoic acid treatment of U937 cells caused the up-regulation of COX1 expression at the protein and mRNA levels. (PMID:12842195)
• expression of COX-1 and COX-2 may influence Amyloid beta peptide generation through mechanisms that involve PG-E2-mediated potentiation of gamma-secretase activity (PMID:14507922)
• differential catalytic regulation of the two PGHS isoforms (PMID:14625295)
• High glucose treatment of THP-1 monocytic cells did no lead to a significant three- to fivefold induction of COX-1 mRNA. (PMID:14988266)
• These studies suggest mPGES-1 colocalizes with both COX-1 and COX-2 to mediate the biosynthesis of PGE2 in the kidney. (PMID:15086459)
• PTGS1 polymorphism may result in an elevated risk of colorectal adenomas. (PMID:15159324)
• cyclooxygenase-1 is induced in synovial cells isolated from rheumatoid arthritis patients, suggesting involvement in the progression of RA (PMID:15167967)
• COX1, but not COX2, is induced during ATRA-dependent maturation and appears to contribute to myeloid differentiation both in vitro and ex vivo, and COX-1 activity may potentiate the differentiation of human acute promyelocytic leukemia (PMID:15190260)
• Expression of COX-1 mRNA was observed in muscle tissues from patients with idiopathic inflammatory myopathies suggesting a role in pathogenesis of this disease. (PMID:15301234)
• Cox1 expression is highly variable in Dukes’ C colorectal tumors and changes in Cox-1 expression may be of importance. (PMID:15328521)
• whereas the mRNA transcript for the spliced COX-1 is present in various human tissues, the corresponding protein is either not formed or subject to rapid proteolytic degradation (PMID:15361066)
• Review of COX 1 expression in squamous cell head and neck neoplasms. (PMID:15375804)
• COX enzymes potentiate inflammatory neuropathology in Alzheimer’s disease (AD) brain. (PMID:15453269)
• COX-1 was observed at each stage of erythroblast development & in mature erythroblasts of the bone marrow. (PMID:15504548)
• cyclooxygenase-2 is increased in peripheral blood mononuclear cells of smokers and patients with hyperlipidemia (PMID:15607906)
• gene expression regulation in Lyme disease (PMID:15654517)
• Estradiol-caused activation of the COX-1 promoter depends on a putative Sp1 binding motif at -89 (relative to the ATG codon) and lesser involvement of a consensus Sp1 site at -111. (PMID:15705965)
• Results showed a stepwise increase in the expression of COX-1 as mucosal damage progressed from normal to gastritis to gastric ulcer. (PMID:15720413)
• Significantly higher expression of cyclooxygenase 1 is associated with metastasis in non-small cell lung cancer (PMID:15870920)
• COX-1 might be a major enzyme regulating PGE2 production in ovarian cancer cells. (PMID:15963707)
• Inducible PGHS-1 gene expression involves the coordinate functioning of a Sp1 site in the promoter and an AP-1 site in intron 8. (PMID:16105649)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptgs1	ENSDARG00000052148
mus_musculus	Ptgs1	ENSMUSG00000047250
rattus_norvegicus	Ptgs1	ENSRNOG00000007415

Paralogs (1): PTGS2 (ENSG00000073756)

Protein

Protein identifiers

Prostaglandin G/H synthase 1 — P23219 (reviewed: P23219)

Alternative names: Cyclooxygenase-1, Prostaglandin H2 synthase 1, Prostaglandin-endoperoxide synthase 1

All UniProt accessions (5): P23219, A0A087X296, A0A2R8Y6S0, A0A2R8YDM0, X6RJD6

UniProt curated annotations — full annotation on UniProt →

Function. Dual cyclooxygenase and peroxidase that plays an important role 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. 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. 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. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. 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.

Subunit / interactions. Homodimer.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane.

Activity regulation. The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac and diclofenac.

Cofactor. Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.

Pathway. Lipid metabolism; prostaglandin biosynthesis.

Miscellaneous. The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site. Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PTGS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PTGS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation. PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer’s disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.

Similarity. Belongs to the prostaglandin G/H synthase family.

Isoforms (6)

UniProt ID	Names	Canonical?
P23219-1	1, Long	yes
P23219-2	2, Short
P23219-3	3
P23219-4	4
P23219-5	5, 1b3
P23219-6	6, 1b2

RefSeq proteins (7): NP_000953, NP_001258093, NP_001258094, NP_001258095, NP_001258296, NP_001258297, NP_542158 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR010255	Haem_peroxidase_sf	Homologous_superfamily
IPR019791	Haem_peroxidase_animal	Family
IPR037120	Haem_peroxidase_sf_animal	Homologous_superfamily
IPR050783	Oxylipin_biosynth_metab	Family

Pfam: PF03098

Enzyme classification (BRENDA):

• EC 1.14.99.1 — prostaglandin-endoperoxide synthase (BRENDA: 16 organisms, 64 substrates, 225 inhibitors, 101 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ARACHIDONATE	0.0009–0.015	33
ARACHIDONIC ACID	0.001–0.16	11
TRANS-5-PHENYL-4-PENTENYL-1-HYDROPEROXIDE	0.02–0.437	8
N,N,N’,N’-TETRAMETHYL-P-PHENYLENEDIAMINE	0.0083–0.0854	5
ALPHA-LINOLENIC ACID	0.0031–0.082	4
CIS-4,7,10,13,16,19-DOCOSAHEXAENOIC ACID	0.0011–0.07	4
CIS-5,8,11,14,17-EICOSAPENTAENOIC ACID	0.0012–0.039	4
CIS-5,8,11,14-EICOSATETRAENOIC ACID	0.0017–0.013	4
CIS-7,10,13,16-DOCOSATETRAENOIC ACID	0.0027–0.061	4
CIS-8,11,14-EICOSATRIENOIC ACID	0.002–0.036	4
O2	0.005–0.011	4
GAMMA-LINOLENIC ACID	0.0048–0.162	3
CIS-11,14-EICOSADIENOIC ACID	0.0052–0.0091	2
GUAIACOL	0.08–0.29	2
H2O2	1.3–5.5	2

Catalyzed reactions (Rhea), 7 shown:

• (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = prostaglandin H2 + A + H2O (RHEA:23728)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2 (RHEA:42596)
• prostaglandin G2 + AH2 = prostaglandin H2 + A + H2O (RHEA:42600)
• (9Z,12Z)-octadecadienoate + AH2 + O2 = (9R)-hydroxy-(10E,12Z)-octadecadienoate + A + H2O (RHEA:75447)
• (9Z,12Z)-octadecadienoate + AH2 + O2 = (13S)-hydroxy-(9Z,11E)-octadecadienoate + A + H2O (RHEA:75451)
• (9Z,12Z)-octadecadienoate + AH2 + O2 = (13R)-hydroxy-(9Z,11E)-octadecadienoate + A + H2O (RHEA:75455)
• (9Z,12Z)-octadecadienoate + AH2 + O2 = (9S)-hydroxy-(10E,12Z)-octadecadienoate + A + H2O (RHEA:75459)

UniProt features (92 total): helix 30, strand 19, sequence variant 10, turn 8, disulfide bond 5, splice variant 5, sequence conflict 4, glycosylation site 3, active site 2, signal peptide 1, chain 1, domain 1, mutagenesis site 1, binding site 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6Y3C	X-RAY DIFFRACTION	3.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23219-F1	94.19	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 206 (proton acceptor); 384 (for cyclooxygenase activity); 529 (aspirin-acetylated serine)

Ligand- & substrate-binding residues (1): 387 (axial binding residue)

Disulfide bonds (5): 35–46, 36–158, 40–56, 58–68, 568–574

Glycosylation sites (3): 67, 103, 143

Mutagenesis-validated functional residues (1):

Position	Phenotype
529	abolishes cyclooxygenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-140180	COX reactions
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

MSigDB gene sets: 347 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, JAEGER_METASTASIS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GNF2_PTX3, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, MODULE_70, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP

GO Biological Process (12): prostaglandin biosynthetic process (GO:0001516), response to oxidative stress (GO:0006979), regulation of blood pressure (GO:0008217), cyclooxygenase pathway (GO:0019371), regulation of cell population proliferation (GO:0042127), long-chain fatty acid biosynthetic process (GO:0042759), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), prostaglandin metabolic process (GO:0006693), prostanoid biosynthetic process (GO:0046457), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (9): peroxidase activity (GO:0004601), prostaglandin-endoperoxide synthase activity (GO:0004666), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), heme binding (GO:0020037), metal ion binding (GO:0046872), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), dioxygenase activity (GO:0051213)

GO Cellular Component (9): photoreceptor outer segment (GO:0001750), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), neuron projection (GO:0043005), extracellular exosome (GO:0070062), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Phase I - Functionalization of compounds	1
Arachidonate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
prostanoid metabolic process	2
oxidoreductase activity	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
response to stress	1
blood circulation	1
regulation of biological quality	1
prostaglandin biosynthetic process	1
arachidonate metabolic process	1
cell population proliferation	1
regulation of cellular process	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
unsaturated fatty acid biosynthetic process	1
icosanoid biosynthetic process	1
cellular detoxification	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	1
dioxygenase activity	1
tetrapyrrole binding	1
cation binding	1
binding	1
catalytic activity	1
photoreceptor cell cilium	1
intracellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGS1	MT-CYB	P00156	896
PTGS1	MT-ND4	P03905	888
PTGS1	MT-ND4L	P03901	885
PTGS1	MT-ATP6	P00846	884
PTGS1	MT-ND3	P03897	884
PTGS1	MT-ND5	P03915	883
PTGS1	MT-ND2	P03891	882
PTGS1	MT-ATP8	P03928	882
PTGS1	MT-ND6	P03923	881
PTGS1	MT-ND1	P03886	880
PTGS1	TBXAS1	P24557	858
PTGS1	COX5B	P10606	763
PTGS1	PTGES	O14684	742
PTGS1	PTGER4	P35408	739
PTGS1	PTGIR	P43119	725

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PTTG1IP	PTGS1	psi-mi:“MI:0915”(physical association)	0.560
NMU	PTGS1	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP3	PTGS1	psi-mi:“MI:0915”(physical association)	0.560
RFFL	PTGS1	psi-mi:“MI:0915”(physical association)	0.560
Dlg4	PTGS1	psi-mi:“MI:0407”(direct interaction)	0.440
	PTGS1	psi-mi:“MI:0915”(physical association)	0.400
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (18): PTGS1 (Affinity Capture-MS), PTGS1 (Affinity Capture-MS), PTGS1 (Proximity Label-MS), PTGS1 (Affinity Capture-MS), PTGS1 (Affinity Capture-MS), PTGS1 (Proximity Label-MS), PTGS1 (Affinity Capture-MS), PTGS1 (Cross-Linking-MS (XL-MS)), PTGIS (FRET), PTGS1 (Protein-RNA), PTGS1 (Affinity Capture-RNA), CAV1 (Affinity Capture-Western), CAV2 (Affinity Capture-Western), PTGS1 (Affinity Capture-Western), PTGS1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1S3ZX38, A0A2G3AC72, B0Y6R2, F9FAJ9, G4N2X9, G4N4J5, G5EB19, O02768, O19183, O61213, O62664, O62698, O62725, O97554, O97598, P05979, P11344, P14679, P22437, P23219, P27607, P35354, P35355, P54834, P55024, P55033, P70682, P79208, Q01603, Q05769, Q2FSF4, Q2QRV3, Q3ATL6, Q4WPX2, Q4WY82, Q5GQ66, Q61419, Q63921, Q6RET3, Q8AVF5

Diamond homologs: A0A1Y9G8H0, A0A452E9Y6, A1XQX2, G5EG78, O02768, O19183, O62664, O62698, O62725, O97554, P05164, P05979, P22079, P22437, P23219, P27607, P35354, P35355, P70682, P79208, P90820, Q05769, Q63921, Q6TMK4, Q8HYB7, Q8HZR1, Q9NRD9, Q8R481, P09933, Q8CIY2, Q8HZK2, Q9ES45, O61213, Q8HZK3, A1XQX0, O94813, Q28146, Q63372, Q9CS84, Q9DDD0

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
“acetylsalicylic acid”	down-regulates	PTGS1	“chemical inhibition”
suprofen	“down-regulates activity”	PTGS1	“chemical inhibition”
ketoprofen	“down-regulates activity”	PTGS1	“chemical inhibition”
oxaprozin	“down-regulates activity”	PTGS1	“chemical inhibition”
ZBTB46	“up-regulates quantity by expression”	PTGS1	“transcriptional regulation”
“5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid”	“down-regulates activity”	PTGS1	“chemical inhibition”
naproxen	“down-regulates activity”	PTGS1	“chemical inhibition”
ibuprofen	“down-regulates activity”	PTGS1	“chemical inhibition”
indometacin	“down-regulates activity”	PTGS1	“chemical inhibition”
PTGS1	“up-regulates quantity”	“prostaglandin G2(1-)”	“chemical modification”
PTGS1	“up-regulates quantity”	“prostaglandin H2(1-)”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

94 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	7
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

2089 predictions. Top by Δscore:

Variant	Effect	Δscore
9:122378773:A:AG	acceptor_gain	1.0000
9:122378773:AGT:A	acceptor_gain	1.0000
9:122378774:G:GA	acceptor_gain	1.0000
9:122378774:GT:G	acceptor_gain	1.0000
9:122378774:GTG:G	acceptor_gain	1.0000
9:122378774:GTGC:G	acceptor_gain	1.0000
9:122381659:CACAG:C	acceptor_loss	1.0000
9:122381661:CAGGT:C	acceptor_loss	1.0000
9:122381662:A:AG	acceptor_gain	1.0000
9:122381662:A:G	acceptor_loss	1.0000
9:122381663:G:GG	acceptor_gain	1.0000
9:122381663:GGT:G	acceptor_gain	1.0000
9:122381663:GGTA:G	acceptor_gain	1.0000
9:122381663:GGTAG:G	acceptor_loss	1.0000
9:122381727:GA:G	donor_gain	1.0000
9:122381743:ACCAG:A	donor_loss	1.0000
9:122381745:CAGGT:C	donor_loss	1.0000
9:122381746:AGG:A	donor_loss	1.0000
9:122381748:G:C	donor_loss	1.0000
9:122381749:T:A	donor_loss	1.0000
9:122383752:ATAG:A	donor_loss	1.0000
9:122383754:AG:A	donor_loss	1.0000
9:122383755:GGTGA:G	donor_loss	1.0000
9:122383756:G:GC	donor_loss	1.0000
9:122386728:GCCGG:G	donor_gain	1.0000
9:122386731:GG:G	donor_gain	1.0000
9:122386732:GG:G	donor_gain	1.0000
9:122386732:GGTAA:G	donor_loss	1.0000
9:122386733:G:GC	donor_loss	1.0000
9:122386733:G:GG	donor_gain	1.0000

AlphaMissense

3949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:122386574:T:C	F380L	0.999
9:122386576:C:A	F380L	0.999
9:122386576:C:G	F380L	0.999
9:122383741:G:C	R332P	0.998
9:122386592:T:A	W386R	0.998
9:122386592:T:C	W386R	0.998
9:122386575:T:C	F380S	0.997
9:122392302:A:C	S520R	0.997
9:122392304:T:A	S520R	0.997
9:122392304:T:G	S520R	0.997
9:122381496:T:C	F208L	0.996
9:122381498:C:A	F208L	0.996
9:122381498:C:G	F208L	0.996
9:122383663:G:C	R306P	0.996
9:122383675:G:C	R310P	0.996
9:122390298:G:C	R466P	0.996
9:122381476:C:A	A201E	0.995
9:122383660:T:C	L305P	0.995
9:122383682:T:G	C312W	0.995
9:122386575:T:G	F380C	0.995
9:122392342:T:C	L533P	0.995
9:122381716:G:C	R244P	0.994
9:122381730:G:T	G249W	0.994
9:122392338:G:C	G532R	0.994
9:122377970:T:A	C56S	0.993
9:122377971:G:C	C56S	0.993
9:122378006:T:A	C68S	0.993
9:122378007:G:C	C68S	0.993
9:122383606:G:A	G287D	0.993
9:122383656:T:A	W304R	0.993

dbSNP variants (sampled 300 via entrez): RS1000008072 (9:122376476 AGG>A), RS1000210449 (9:122396187 T>C), RS1000495531 (9:122388494 T>A), RS1000514376 (9:122384766 G>C), RS1000566651 (9:122385045 C>A), RS1000705368 (9:122391213 T>G), RS1000802371 (9:122379688 G>A), RS1001101213 (9:122391007 A>C), RS1001137979 (9:122372672 C>G), RS1001170411 (9:122391302 A>T), RS1001228171 (9:122382375 G>A), RS1001422369 (9:122372951 G>C), RS1001497042 (9:122394660 G>A,C), RS1001761026 (9:122388063 G>A), RS1001915802 (9:122372994 C>T)

Disease associations

OMIM: gene MIM:176805 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
platelet-type bleeding disorder 12	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
platelet-type bleeding disorder 12	Limited	SD

Mondo (1): platelet-type bleeding disorder 12 (MONDO:0011588)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003139_11	Glomerular filtration rate in chronic kidney disease	4.000000e-06
GCST010396_99	Gut microbiota (bacterial taxa, hurdle binary method)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567786	Prostaglandin-Endoperoxide Synthase 1 Deficiency, Platelet (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2094253 (PROTEIN FAMILY), CHEMBL221 (SINGLE PROTEIN), CHEMBL4523964 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

272 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,571,483 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL118	CELECOXIB	4	112,844
CHEMBL25	ASPIRIN	4	694,602
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL622	ETODOLAC	4	57,872
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1020	TOLMETIN	4	60,332
CHEMBL1027	TIAGABINE	4	12,112
CHEMBL1034	DICLOFENAC SODIUM	4	45,460
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1077	BROMFENAC	4	12,495
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL1098319	2-MERCAPTOETHANESULFONIC ACID	4	6,507
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1136	TELITHROMYCIN	4	15,927
CHEMBL1138	EZETIMIBE	4	29,509
CHEMBL1161	MOMETASONE FUROATE	4	25,884
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL117287	PRUCALOPRIDE	4
CHEMBL119	TRIMETREXATE	4
CHEMBL1200971	CEPHALOGLYCIN	4
CHEMBL1200973	ESTRADIOL CYPIONATE	4
CHEMBL1200979	DEXPANTHENOL	4
CHEMBL1201016	CEFPODOXIME PROXETIL	4
CHEMBL1201196	SERTACONAZOLE	4
CHEMBL1201334	TRIPTORELIN	4
CHEMBL1219	RABEPRAZOLE	4
CHEMBL122	ROFECOXIB	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10306114	Efficacy	3	latanoprost	Open-angle glaucoma
rs10306114	Efficacy	3	aspirin;clopidogrel	Myocardial Infarction
rs10306114	Efficacy	3	aspirin	Coronary Artery Disease;Myocardial Infarction
rs10306135	Toxicity	3	Antiinflammatory agents;non-steroids	Acute coronary syndrome
rs1330344	Efficacy	3	clopidogrel	Major Adverse Cardiac Events (MACE)

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5788	PTGS1		0.00	0
rs5789	PTGS1		0.00	0
rs1236913	PTGS1		0.00	0
rs3842787	PTGS1		0.00	0
rs10306114	PTGS1	3	6.00	3	aspirin;clopidogrel;aspirin;latanoprost
rs10306135	PTGS1	3	3.25	1	Antiinflammatory agents;non-steroids
rs12353214	PTGS1		0.00	0
rs1330344	PTGS1	3	2.25	1	clopidogrel

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Cyclooxygenase

Most potent curated ligand interactions (32 total), top 25:

Ligand	Action	Affinity	Parameter
(S)-ARN2508	Inhibition	9.54	pIC50
FK-881	Inhibition	8.31	pIC50
bromfenac	Inhibition	8.07	pIC50
SC-560	Inhibition	8.05	pIC50
diclofenac	Inhibition	7.92	pIC50
FR122047	Inhibition	7.5	pIC50
meclofenamic acid	Inhibition	7.3	pIC50
flurbiprofen	Inhibition	7.12	pIC50
fenoprofen	Inhibition	6.84	pIC50
indomethacin	Inhibition	6.59	pIC50
ketoprofen	Inhibition	6.48	pIC50
suprofen	Inhibition	6.25	pIC50
SWE101	Inhibition	5.92	pIC50
sulindac	Inhibition	5.92	pIC50
piroxicam	Inhibition	5.89	pIC50
oxaprozin	Inhibition	5.66	pIC50
ibuprofen	Inhibition	5.52	pIC50
phenylbutazone	Inhibition	5.52	pIC50
naproxen	Inhibition	5.49	pIC50
(R)-ARN2508	Inhibition	5.4	pIC50
peptide 30 [PMID: 27019010]	Inhibition	5.22	pIC50
celecoxib	Inhibition	4.82	pIC50
nimesulide	Inhibition	4.76	pIC50
SC-236	Inhibition	4.75	pIC50
mefenamic acid	Inhibition	4.6	pIC50

Binding affinities (BindingDB)

34 measured of 104 human assays (113 total across all organisms); most potent 34 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
dexamethasone (tetramethyl-rhodamine conjugated )	EC50	0.2 nM
CHEMBL5270291	IC50	25 nM
5-Chloro-3-(4-methanesulfonyl-phenyl)-6’’-methyl-[2,3’’]bipyridinyl	KI	79 nM
5-Chloro-2-oxo-3-(thiophene-2-carbonyl)-2,3-dihydro-indole-1-carboxylic acid amide(tenidap)	KI	81 nM
Rimadyl	KI	87 nM
nimesulide	KI	120 nM
ARTHROTEC	KI	150 nM
CHEMBL5269189	IC50	370 nM
Zomepirac	KI	430 nM
2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid	IC50	980 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetic acid	KI	1080 nM
2-[4-(thiophen-2-ylcarbonyl)phenyl]propanoic acid	KI	1100 nM
Lodine	KI	1200 nM
NSC_4856	KI	2400 nM
CAS_530-78-9	KI	3000 nM
NS398	KI	6900 nM
NSC_53454	KI	7600 nM
4-[3-(4-methoxyphenyl)-5-phenyl-3,4-dihydropyrazol-2-yl]benzenesulfonamide	EC50	8040 nM
CHEMBL4790503	IC50	8990 nM
2-(6-methoxynaphthalen-2-yl)propanoic acid	KI	9300 nM
salicylic acid	KI	9900 nM
4-Hydroxy-1,1-dioxo-1,2-dihydro-1lambda6-benzo[e][1,2]thiazine-3-carboxylic acid (5-methyl-thiazol-2-yl)-amide	KI	10100 nM
benzimidazol-2-yl)piperidin-1-	IC50	11700 nM	US-11478464: Method for treating inflammation
CHEMBL4788670	IC50	11800 nM
4-acetyl-2-(2-carboxyanilino)benzoic acid	IC50	27700 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-(acetyloxy)benzoic acid	EC50	30000 nM
{6-Fluoro-2-methyl-3-[1-(4-methylsulfanyl-phenyl)-meth-(E)-ylidene]-3H-inden-1-yl}-acetic acid	EC50	30000 nM
calcium;2-(3-phenoxyphenyl)propanoic acid;hydrate	EC50	30000 nM
2-(6-methoxynaphthalen-2-yl)ethanoic acid	EC50	30000 nM
UNM-0000306136	EC50	30000 nM
3-[N-(4-chlorophenyl)amino]benzoic acid	IC50	30200 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
3-[N-(4-acetylphenyl)amino]benzoic acid	IC50	38600 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-(5-methoxy-2-nitroanilino)benzoic acid	IC50	42700 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-[2-nitro-5-(trifluoromethyl)anilino]benzoic acid	IC50	50000 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof

ChEMBL bioactivities

1495 potent at pChembl≥5 of 2578 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.85	IC50	0.14	nM	INDOMETHACIN
9.00	IC50	1	nM	CHEMBL5206077
9.00	IC50	1	nM	CHEMBL143776
8.91	IC50	1.23	nM	CHEMBL1945285
8.85	IC50	1.4	nM	MOFEZOLAC
8.72	IC50	1.9	nM	DEXKETOPROFEN
8.70	IC50	2	nM	INDOMETHACIN
8.70	IC50	2	nM	KETOPROFEN
8.70	IC50	2	nM	CHEMBL1232083
8.70	IC50	2	nM	CHEMBL314337
8.52	IC50	3	nM	DICLOFENAC
8.52	IC50	3	nM	DICLOFENAC SODIUM
8.52	AC50	3	nM	FLURBIPROFEN
8.52	IC50	3	nM	INDOMETHACIN
8.43	AC50	3.7	nM	DEXKETOPROFEN
8.40	IC50	4	nM	CHEMBL5184826
8.40	IC50	4	nM	DICLOFENAC SODIUM
8.35	IC50	4.483	nM	DEXKETOPROFEN
8.31	IC50	4.9	nM	CHEMBL3427203
8.30	IC50	5	nM	CHEMBL29204
8.30	IC50	5	nM	INDOMETHACIN
8.30	IC50	5	nM	CHEMBL3427203
8.30	IC50	5	nM	CHEMBL5192908
8.30	IC50	5	nM	CHEMBL432945
8.29	IC50	5.19	nM	VORTIOXETINE
8.28	IC50	5.3	nM	CARPROFEN
8.24	IC50	5.7	nM	PRIFELONE
8.22	IC50	6	nM	INDOMETHACIN
8.17	AC50	6.7	nM	BROMFENAC
8.15	IC50	7	nM	DUP-697
8.15	IC50	7	nM	LUMIRACOXIB
8.15	IC50	7	nM	SC-560
8.15	IC50	7	nM	CHEMBL80405
8.11	IC50	7.8	nM	SC-560
8.10	IC50	7.9	nM	MOFEZOLAC
8.10	IC50	8	nM	CHEMBL4476621
8.10	IC50	8	nM	SC-560
8.09	IC50	8.2	nM	INDOMETHACIN
8.07	IC50	8.481	nM	BROMFENAC
8.05	IC50	9	nM	SC-560
8.05	IC50	8.9	nM	SC-560
8.03	IC50	9.4	nM	ETODOLAC
8.00	IC50	10	nM	CHEMBL16996
8.00	IC50	10	nM	FLURBIPROFEN
8.00	IC50	10	nM	INDOMETHACIN
8.00	IC50	10	nM	ACEMETACIN
8.00	IC50	10	nM	SC-560
8.00	IC50	10	nM	CHEMBL1241992
7.96	IC50	11	nM	CHEMBL5273339
7.96	IC50	11	nM	SC-560

PubChem BioAssay actives

997 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Indomethacin	1993609: Inhibition of COX1 (unknown origin)	ic50	0.0001	uM
4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)pyrazol-5-yl]benzenesulfonamide	161494: In vitro inhibitory concentration required to block recombinant human prostaglandin G/H synthase 1 (COX-1)	ic50	0.0010	uM
1-(4-methoxyphenyl)-5-(4-(111C)methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1,2,4-triazole	1896005: Inhibition of human COX1	ic50	0.0010	uM
(2S)-3-fluoro-2-[4-(2-methylpropyl)phenyl]propanoic acid	642830: Inhibition of COX1 in human HEL 92.1.7 cells assessed as thromboxane B2 production incubated for 30 mins before arachidonic acid addition measured after 15 mins by ELISA	ic50	0.0012	uM
2-[3,4-bis(4-methoxyphenyl)-1,2-oxazol-5-yl]acetic acid	1709972: Inhibition of COX1 (unknown origin)	ic50	0.0014	uM
3-[1-[(4-chlorophenyl)methyl]-3-(3,3-dimethylbutanoyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	160848: The compound was tested for inhibitory activity against Prostaglandin G/H synthase in human polymorphonuclear leukocytes[PMNS]	ic50	0.0020	uM
Ketoprofen	2016825: Inhibition of COX-1 in human platelet in presence of arachidonic acid by human whole blood assay	ic50	0.0020	uM
(2R)-6,8-dichloro-7-(2-methylpropoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid	547805: Inhibition of human COX1	ic50	0.0020	uM
Diclofenac	664063: Inhibition of COX1	ic50	0.0030	uM
3-[dideuterio(fluoro)methoxy]-1,5-bis(4-methoxyphenyl)-1,2,4-triazole	1896005: Inhibition of human COX1	ic50	0.0040	uM
Diclofenac Sodium	2016828: Inhibition of human recombinant COX-1 transfected in CHO cells assessed as inhibition of arachidonic acid-stimulated PGE2 production preincubated for 15 mins followed by arachidonic acid addition and measured after 15 mins by chromogenic assay	ic50	0.0040	uM
1,5-bis(4-methoxyphenyl)-3-(trifluoromethyl)pyrazole	161494: In vitro inhibitory concentration required to block recombinant human prostaglandin G/H synthase 1 (COX-1)	ic50	0.0050	uM
4-[5-(4-methoxyphenyl)spiro[2.4]hept-5-en-6-yl]benzenesulfonamide	161661: Inhibitory activity against prostaglandin G/H synthase 1 (COX-1).	ic50	0.0050	uM
3-(111C)methoxy-1,5-bis(4-methoxyphenyl)-1,2,4-triazole	1896005: Inhibition of human COX1	ic50	0.0050	uM
Carprofen	1993616: Inhibition of human COX1	ic50	0.0053	uM
2-[2-(2-chloro-6-fluoroanilino)-5-methylphenyl]acetic acid	664063: Inhibition of COX1	ic50	0.0070	uM
5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene	161500: Inhibition of Prostaglandin G/H synthase 1 was measured by the inhibition of PGE-2 produced by microsomes from U937 cells at subsaturating arachidonic acid conc.	ic50	0.0070	uM
5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)pyrazole	161494: In vitro inhibitory concentration required to block recombinant human prostaglandin G/H synthase 1 (COX-1)	ic50	0.0070	uM
1-(3,4-dichlorophenyl)-3-[(2-hydroxybenzoyl)amino]thiourea	1584855: Inhibition of human recombinant COX1 using arachidonic acid as substrate after 3 mins by fluorimetric analysis	ic50	0.0080	uM
Etodolac	1993616: Inhibition of human COX1	ic50	0.0094	uM
2-[2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetyl]oxyacetic acid	1993609: Inhibition of COX1 (unknown origin)	ic50	0.0100	uM
Flurbiprofen	313126: Inhibition of COX1	ic50	0.0100	uM
4-[2-(benzylamino)-4-(3-fluoro-4-methoxyphenyl)-1,3-thiazol-5-yl]benzenesulfonamide	161333: Inhibition of human Prostaglandin G/H synthase 1	ic50	0.0100	uM
disodium;(1Z)-3-methoxy-N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonyl-4-oxidobenzenecarboximidate	1936407: Inhibition of COX1 (unknown origin)	ic50	0.0110	uM
4-[(E)-2-[3-[(E)-2-[4-hydroxy-3-methoxy-5-(3-methylbut-2-enyl)phenyl]ethenyl]-1H-pyrazol-5-yl]ethenyl]-2-methoxy-6-(3-methylbut-2-enyl)phenol	1155597: Inhibition of COX1-mediated PGF2alpha formation in LPS-stimulated human monocytes preincubated for 15 mins before arachidonic acid substrate addition measured after 30 mins by UPLC-MS/MS analysis	ic50	0.0130	uM
Celecoxib	1936407: Inhibition of COX1 (unknown origin)	ic50	0.0130	uM
1-(4-chlorophenyl)-5-(4-methoxyphenyl)-3-(trifluoromethyl)pyrazole	161494: In vitro inhibitory concentration required to block recombinant human prostaglandin G/H synthase 1 (COX-1)	ic50	0.0180	uM
2-[2-(2-benzofuran-1-yl)-6,6-dimethyl-1-phenyl-5,7-dihydropyrrolizin-3-yl]acetic acid	1953438: Inhibition of COX1 (unknown origin)	ic50	0.0200	uM
7-tert-butyl-3,3-dimethyl-5-[(Z)-2-thiophen-2-ylethenyl]-2H-1-benzofuran	161655: Inhibitory activity against prostaglandin G/H synthase 1 (COX-1)	ic50	0.0200	uM
9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0230	uM
disodium;(E,1Z)-3-(3-methoxy-4-oxidophenyl)-N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylprop-2-enimidate	1936407: Inhibition of COX1 (unknown origin)	ic50	0.0230	uM
sodium [4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonyl-[2-[4-(2-methylpropyl)phenyl]propanoyl]azanide	1936407: Inhibition of COX1 (unknown origin)	ic50	0.0250	uM
9-[(4-chlorophenyl)methyl]-6-methylsulfonyl-1,2,3,4-tetrahydrocarbazole	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0270	uM
9-(4-chlorophenyl)sulfonyl-6-methylsulfonyl-1,2,3,4-tetrahydrocarbazole	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0280	uM
[4,5-bis(4-methoxyphenyl)-1,3-thiazol-2-yl]-(4-methylpiperazin-1-yl)methanone	328205: Inhibition of COX1	ic50	0.0280	uM
7-(4-methylphenyl)-6-(4-methylsulfanylphenyl)-2,3-dihydro-1H-pyrrolizine	1953438: Inhibition of COX1 (unknown origin)	ic50	0.0300	uM
9-[(4-chlorophenyl)methyl]-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0330	uM
2,6-ditert-butyl-4-[(E)-2-thiophen-2-ylethenyl]phenol	160844: Inhibition of human platelet Prostaglandin G/H synthase	ic50	0.0340	uM
9-(4-chlorophenyl)sulfonyl-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0340	uM
(7-tert-butyl-3,3-dimethyl-2H-1-benzofuran-5-yl)-(1-methylpyrrol-2-yl)methanone	161655: Inhibitory activity against prostaglandin G/H synthase 1 (COX-1)	ic50	0.0350	uM
sodium ethoxycarbonyl-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylazanide	1936407: Inhibition of COX1 (unknown origin)	ic50	0.0350	uM
3-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]-1-(4-methoxyphenyl)-5-phenylpyrazole	281535: Inhibition of COX1 expressed in CHO cells assessed as inhibition of arachidonic acid-stimulated PGE2 production by enzyme immunoassay	ic50	0.0360	uM
(4-chlorophenyl)-(6-methylsulfonyl-1,2,3,4-tetrahydrocarbazol-9-yl)methanone	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0380	uM
2-[1-(7-chloroquinolin-4-yl)-5-methoxy-2-methylindol-3-yl]acetic acid	268670: Inhibition of COX1-mediated platelet aggregation	ic50	0.0400	uM
6-chloro-N-(2-chlorophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1lambda6,2-benzothiazine-4-carboxamide	161467: Concentration of drug that causes a 50% decrease in the maximal inhibition of Prostaglandin G/H synthase 1 activity as measured by PGE2 production(’+’ indicates 90-110% inhibition)	ic50	0.0410	uM
9-(4-chlorophenyl)sulfonyl-6-methoxy-2,2-dimethyl-1,3-dihydrocarbazol-4-one	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0410	uM
2-(5-benzoyl-2-methoxyphenyl)propanoic acid	161469: Concentration required for 50% inhibition against Prostaglandin G/H synthase 1 from human	ic50	0.0420	uM
9-[(4-chlorophenyl)methyl]-6-methoxy-2,2-dimethyl-1,3-dihydrocarbazol-4-one	1503676: Inhibition of human kidney microsomal COX assessed as PGE2 level using arachidonic acid as substrate preincubated for 5 to 15 mins followed by substrate addition measured after 40 mins by radio immunoassay	ic50	0.0440	uM
5-[4-[3-[1-(4-methoxyphenyl)-5-(4-methylphenyl)pyrazol-3-yl]propanoylamino]butylcarbamoyl]-2-(3-oxa-23-aza-9-azoniaheptacyclo[17.7.1.15,9.02,17.04,15.023,27.013,28]octacosa-1(27),2(17),4,9(28),13,15,18-heptaen-16-yl)benzoate	1724966: Inhibition of COX-1 in human OVCAR3 cells assessed as [14C] arachidonic acid remaining using [14C] arachidonic acid as substrate preincubated for 30 mins followed by substrate addition measured after 30 mins	ic50	0.0440	uM
(7-tert-butyl-3,3-dimethyl-2H-1-benzofuran-5-yl)-thiophen-2-ylmethanone	161655: Inhibitory activity against prostaglandin G/H synthase 1 (COX-1)	ic50	0.0450	uM

CTD chemical–gene interactions

183 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aspirin	decreases activity, decreases reaction, increases activity, decreases expression, increases acetylation (+6 more)	10
Indomethacin	affects binding, decreases reaction, increases chemical synthesis, decreases expression, increases expression (+2 more)	8
Tretinoin	decreases reaction, increases expression, decreases expression	6
SC 560	decreases activity, decreases reaction, increases activity	4
Resveratrol	decreases reaction, increases activity, decreases activity, decreases expression	4
Acetaminophen	decreases activity, decreases expression	4
Estradiol	affects expression, affects cotreatment, increases expression	4
Arachidonic Acid	decreases reaction, increases chemical synthesis, increases metabolic processing, increases activity, increases response to substance (+1 more)	4
bisphenol A	affects cotreatment, affects expression, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	decreases activity, increases expression, increases reaction	3
monomethylarsonous acid	affects expression, decreases expression, increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	3
Cisplatin	affects expression, increases expression, affects response to substance	3
Dexamethasone	decreases reaction, increases expression, affects cotreatment, decreases expression	3
Ethinyl Estradiol	affects expression, decreases expression	3
Ibuprofen	decreases activity	3
Lipopolysaccharides	affects cotreatment, decreases reaction, increases expression, decreases expression	3
Progesterone	affects cotreatment, increases expression	3
Dinoprostone	increases reaction, decreases reaction, increases chemical synthesis, increases abundance	3
mercuric bromide	decreases expression, affects cotreatment	2
rofecoxib	decreases activity, decreases expression	2
cotylenin A	increases expression, increases reaction	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Arsenic Trioxide	decreases expression, decreases reaction, increases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Calcitriol	increases expression	2
Diclofenac	decreases activity, decreases expression, affects cotreatment	2
Diethylhexyl Phthalate	affects expression, affects reaction, decreases expression, affects cotreatment	2

ChEMBL screening assays

958 unique, capped per target: 878 binding, 42 functional, 38 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2038420	Binding	Inhibition of cyclooxygenase-mediated PGE2 production in human HT-29 cells at 1 uM after 25 hrs by LC-MS/MS analysis	Radiosynthesis of a ¹⁸F-labeled 2,3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo. — Bioorg Med Chem
CHEMBL4273610	ADMET	Modulation of COX1/2-mediated PGF2a level in human M1 macrophages derived from LPS/IFNgamma-polarized human monocyte derived macrophages at 3 uM preincubated for 15 mins followed by Escherichia coli (O6:K2:H1) challenge for 90 mins by LC-MS	Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation. — Eur J Med Chem
CHEMBL660374	Functional	Half-maximal inhibition of the COX activity was measured by the direct analysis of the consumed O2 using isolated sheep seminal vesicles	New indene-derivatives with anti-proliferative properties. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8NC	Abcam HCT 116 PTGS1 KO	Cancer cell line	Male
CVCL_B9AU	Abcam MCF-7 PTGS1 KO	Cancer cell line	Female
CVCL_B9QM	Abcam A-549 PTGS1 KO	Cancer cell line	Male
CVCL_E1FK	Abcam A-431 PTGS1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.