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
• GTEx eGene: eQTL in 23 tissues, sQTL in 6 (q < 0.05)
• Drug target: yes — 3 curated mechanism-of-action drugs, 49 via a complex or family; 272 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 2 — Alclofenac, Mofezolac
• Approved drugs acting on a complex or family including it: 43 — Acemetacin, Acetaminophen, Aspirin, +40 more (Cyclooxygenase)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.82 (unconstrained)
• MANE Select transcript: NM_000962
• Interaction hub: 1,988 STRING partners (top 8% of genes corpus-wide)
• Notable: 94 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 21 — 15 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000362012

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 5: 2

ENST00000362012, ENST00000223423, ENST00000373698, ENST00000426608, ENST00000540753, ENST00000619306, ENST00000643576, ENST00000643810, ENST00000645132, ENST00000647067, ENST00000863389, ENST00000863390, ENST00000863391, ENST00000863392, ENST00000863393, ENST00001001984, ENST00001001985, ENST00001001986, ENST00001035925, ENST00001107510, ENST00001134935

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.

Highest expression (Bgee): stromal cell of endometrium, germinal epithelium of ovary, monocyte, upper arm skin, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PTGS1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	9.1e-19	+0.77	9:122384199:C:T
Esophagus Gastroesophageal Junction	eqtl	3.7e-13	+0.72	9:122373512:C:T
Cells Cultured fibroblasts	eqtl	4.6e-13	+0.34	9:122427311:G:A
Esophagus Muscularis	eqtl	9.8e-13	+0.58	9:122373512:C:T
Artery Tibial	eqtl	1.2e-11	+0.33	9:122387679:T:C
Esophagus Mucosa	eqtl	7.2e-11	+0.53	9:122369748:A:G
Thyroid	eqtl	6.6e-10	+0.31	9:122387679:T:C
Heart Atrial Appendage	eqtl	1.2e-09	+0.39	9:122383050:G:C
Skin Sun Exposed Lower leg	sqtl	5.0e-09	-1.86	9:122390342:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-07	-0.15	9:122369409:C:T
Muscle Skeletal	eqtl	3.0e-06	+0.20	9:122387679:T:C
Cells Cultured fibroblasts	sqtl	1.7e-05	-0.25	9:122387724:T:G
Skin Sun Exposed Lower leg	eqtl	5.7e-05	-0.12	9:122369409:C:T
Adipose Subcutaneous	eqtl	6.5e-05	+0.19	9:122383050:G:C
Esophagus Mucosa	sqtl	1.9e-04	-1.62	9:122390342:G:A
Stomach	eqtl	2.2e-04	+0.54	9:122373512:C:T
Skin Not Sun Exposed Suprapubic	sqtl	2.7e-04	-0.40	9:122383464:T:C
Whole Blood	eqtl	3.3e-04	-0.13	9:122427311:G:A
Artery Coronary	eqtl	3.6e-04	+0.54	9:122382662:T:C
Whole Blood	sqtl	5.5e-04	-0.36	9:122375416:A:T

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

showing 100 of 288 tissues 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
esophagus mucosa	UBERON:0002469	90.89	gold quality
penis	UBERON:0000989	90.82	gold quality
pharyngeal mucosa	UBERON:0000355	90.81	gold quality
right uterine tube	UBERON:0001302	90.41	gold quality
blood	UBERON:0000178	88.96	gold quality
fallopian tube	UBERON:0003889	88.96	gold quality
fundus of stomach	UBERON:0001160	88.91	gold quality
colon	UBERON:0001155	88.51	gold quality
granulocyte	CL:0000094	88.38	gold quality
large intestine	UBERON:0000059	88.35	gold quality
oviduct epithelium	UBERON:0004804	88.20	gold quality
rectum	UBERON:0001052	87.99	gold quality
mammalian vulva	UBERON:0000997	87.88	gold quality
smooth muscle tissue	UBERON:0001135	87.76	gold quality
colonic epithelium	UBERON:0000397	87.70	gold quality
pylorus	UBERON:0001166	86.81	gold quality
intestine	UBERON:0000160	86.72	gold quality
transverse colon	UBERON:0001157	86.56	gold quality
cervix epithelium	UBERON:0004801	86.17	gold quality
visceral pleura	UBERON:0002401	85.80	gold quality
body of stomach	UBERON:0001161	85.78	gold quality
trabecular bone tissue	UBERON:0002483	85.51	gold quality
endometrium	UBERON:0001295	84.97	gold quality
cardiac muscle of right atrium	UBERON:0003379	84.97	gold quality
vermiform appendix	UBERON:0001154	84.94	gold quality
endothelial cell	CL:0000115	84.92	silver quality
stomach	UBERON:0000945	84.82	gold quality
superficial temporal artery	UBERON:0001614	84.38	silver quality
caecum	UBERON:0001153	83.99	gold quality
myocardium	UBERON:0002349	83.53	gold quality
cardia of stomach	UBERON:0001162	83.52	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.47	gold quality
small intestine	UBERON:0002108	83.33	gold quality
gingival epithelium	UBERON:0001949	82.91	gold quality
gall bladder	UBERON:0002110	82.76	gold quality
amniotic fluid	UBERON:0000173	82.65	gold quality
oral cavity	UBERON:0000167	82.58	gold quality
epithelial cell of pancreas	CL:0000083	82.57	silver quality
cardiac atrium	UBERON:0002081	82.46	gold quality
gingiva	UBERON:0001828	82.43	gold quality
right atrium auricular region	UBERON:0006631	82.05	gold quality
periodontal ligament	UBERON:0008266	81.89	gold quality
layer of synovial tissue	UBERON:0007616	81.81	gold quality
synovial joint	UBERON:0002217	81.66	gold quality
pericardium	UBERON:0002407	81.27	gold quality
left uterine tube	UBERON:0001303	81.25	gold quality
duodenum	UBERON:0002114	80.91	gold quality
peritoneum	UBERON:0002358	80.89	gold quality
omental fat pad	UBERON:0010414	80.87	gold quality
vena cava	UBERON:0004087	80.82	silver quality
mucosa of transverse colon	UBERON:0004991	80.57	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.48	gold quality
bone marrow	UBERON:0002371	80.37	gold quality
vagina	UBERON:0000996	80.31	gold quality
upper lobe of left lung	UBERON:0008952	80.26	gold quality
medial globus pallidus	UBERON:0002477	80.12	gold quality
right coronary artery	UBERON:0001625	80.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.00	gold quality
right lung	UBERON:0002167	79.99	gold quality
upper lobe of lung	UBERON:0008948	79.73	gold quality
uterus	UBERON:0000995	79.03	gold quality
bone marrow cell	CL:0002092	79.01	gold quality
colonic mucosa	UBERON:0000317	78.94	gold quality
jejunal mucosa	UBERON:0000399	78.71	gold quality
globus pallidus	UBERON:0001875	78.68	gold quality
left ventricle myocardium	UBERON:0006566	78.28	gold quality
epithelium of nasopharynx	UBERON:0001951	78.06	gold quality
inferior vagus X ganglion	UBERON:0005363	77.70	gold quality
renal medulla	UBERON:0000362	77.68	gold quality
uterine cervix	UBERON:0000002	77.65	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	144.0	high
Esophagus	tissue	63.2	medium
Urinary bladder	tissue	60.5	low
Fallopian tube	tissue	40.7	high
Rectum	tissue	22.8	high
Colon	tissue	18.9	high
Prostate	tissue	18.5	not detected
Stomach 1	tissue	16.8	low
Smooth muscle	tissue	15.0	medium
Hippocampus	tissue	15.0	medium
Small intestine	tissue	13.8	high
Frontal cortex	tissue	12.9
Vagina	tissue	12.0	low
Choroid plexus	tissue	12.0
Caudate putamen	tissue	11.1
Tonsil	tissue	10.9	high
Lung	tissue	10.6	high
Spinal cord	tissue	10.5
Duodenum	tissue	10.2	high
Appendix	tissue	9.9	high
Gallbladder	tissue	9.0	low
Hypothalamus	tissue	8.8
Kidney	tissue	8.7	low
Bone marrow	tissue	8.5	medium
Locus coeruleus	tissue	8.4
Periaqueductal gray	tissue	8.2
Medulla oblongata	tissue	7.8
Pons	tissue	7.7
Substantia nigra	tissue	7.6
Septum	tissue	7.5
Breast	tissue	6.3	low
Adipose tissue	tissue	5.9	not detected
Seminal vesicle	tissue	5.8	medium
Spleen	tissue	5.8	not detected
Heart muscle	tissue	5.7	not detected
Endometrium 1	tissue	5.7	high
Superior colliculi	tissue	5.4
Ventral forebrain	tissue	5.1
Midbrain	tissue	5.0
Thalamus	tissue	4.9
Amygdala	tissue	4.8
Lymph node	tissue	4.3	medium
Putamen	tissue	4.0
Nucleus accumbens	tissue	4.0
Cervix	tissue	3.9	medium
Pituitary gland	tissue	3.8
Tongue	tissue	3.8
Corpus callosum	tissue	3.8
Hippocampal formation	tissue	3.7
Basal ganglia	tissue	3.4	medium
Entorhinal cortex	tissue	2.9
Cerebral cortex	tissue	2.8	medium
Liver	tissue	2.8	low
Adrenal gland	tissue	2.8	not detected
Insular cortex	tissue	2.8
Salivary gland	tissue	2.7	not detected
Temporal cortex	tissue	2.7
Prefrontal cortex	tissue	2.6
Motor cortex	tissue	2.5
Olfactory bulb	tissue	2.4

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Lateral funiculus (white matter) (26.2), Hippocampus, CA2 (15.8), Nucleus rhomboideus (15.2), Cervical spinal cord, ventral horn (14.9), Dentate gyrus (14.9).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting PTGS1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 107 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.74e-09, LOEUF 0.82, missense Z 1.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000362012 — one region, missense o/e 0.90.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97797) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 50 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased prostaglandin level	7
decreased physiological sensitivity to xenobiotic	3
decreased inflammatory response	2
increased susceptibility to induced colitis	2
decreased platelet aggregation	2
decreased urine prostaglandin level	2
delayed parturition	2
abnormal blood flow velocity	1
abnormal cecum morphology	1
decreased digestive secretion	1
enlarged spleen	1
abnormal drinking behavior	1
increased thermal nociceptive threshold	1
increased cellular sensitivity to gamma-irradiation induced cell death	1
abnormal kidney morphology	1
abnormal blood coagulation	1
abnormal keratinocyte differentiation	1
abnormal corpus luteum morphology	1
abnormal nociception after inflammation	1
abnormal parturition	1
allodynia	1
decreased susceptibility to induced arthritis	1
abnormal response/metabolism to endogenous compounds	1
maternal effect	1
abnormal uterine environment	1

+25 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	O62664	97.7%	Diamond
Ovis aries	P05979	97.7%	Diamond
Canis lupus familiaris	Q8HZR1	92.9%	Diamond
Oryctolagus cuniculus	O97554	91.4%	Diamond
Equus caballus	O19183	90.9%	Diamond
Cavia porcellus	P70682	90.2%	Diamond
Neogale vison	O62725	89.6%	Diamond
Sus scrofa	Q8HZK2	85.7%	Diamond
Gallus gallus	P27607	82.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
OR1J4	protein-coding	26219
OR1J2	protein-coding	26740
OR1J1	protein-coding	347168
MRRF	protein-coding	92399
MORN5	protein-coding	254956
LHX6	protein-coding	26468
RBM18	protein-coding	92400
OR1L8	protein-coding	138881
OR1N2	protein-coding	138882
OR1N1	protein-coding	138883
OR1Q1	protein-coding	158131

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): A0A087X296, A0A2R8Y6S0, A0A2R8YDM0, P23219, 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)

• (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 (99 total): helix 38, strand 18, 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 by resolution:

PDB	Title	Method	Resolution (Å)
6Y3C	Human COX-1 Crystal Structure	X-RAY DIFFRACTION	3.36

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; vesicles

Antibody reliability (HPA): IH enhanced · IF uncertain

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)

Position	Role
206	proton acceptor
384	for cyclooxygenase activity
529	aspirin-acetylated serine

Ligand- & substrate-binding residues (1)

Position	Role
387	heme b

Disulfide bonds (5)

Type	Positions
Disulfide bond	35–46, 36–158, 40–56, 58–68, 568–574

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	67, 103, 143

Mutagenesis-validated functional residues (1)

Position	Phenotype
529	abolishes cyclooxygenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-140180	COX reactions	curated
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	curated
R-HSA-2142753	Arachidonate metabolism	—
R-HSA-211859	Biological oxidations	—
R-HSA-8978868	Fatty acid metabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-211945	Phase I - Functionalization of compounds	—

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 (10): prostaglandin biosynthetic process (GO:0001516), response to oxidative stress (GO:0006979), regulation of blood pressure (GO:0008217), cyclooxygenase pathway (GO:0019371), 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 (7): 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), endomembrane system (GO:0012505)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Metabolism	2
Phase I - Functionalization of compounds	1
Arachidonate metabolism	1
Biological oxidations	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

39 GO namespaces:

Category	Terms
cellular anatomical structure	3
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
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
extracellular vesicle	1
vacuole	1
plasma membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
cyclooxygenase pathway	BP	direct assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
prostaglandin-endoperoxide synthase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,988 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGS1	MT-ND4L	P03901	883
PTGS1	MT-ATP6	P00846	882
PTGS1	MT-ND2	P03891	882
PTGS1	MT-ND3	P03897	882
PTGS1	MT-ND4	P03905	882
PTGS1	MT-ND5	P03915	882
PTGS1	MT-ND6	P03923	882
PTGS1	MT-ATP8	P03928	882
PTGS1	MT-ND1	P03886	881
PTGS1	TBXAS1	P24557	860
PTGS1	MT-CYB	P00156	857
PTGS1	COX4I2	Q96KJ9	834
PTGS1	COX4I1	P13073	829
PTGS1	COX5A	P20674	819
PTGS1	COX5B	P10606	811

IntAct

Human interaction partners of PTGS1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
ARFGAP3	physical association	0.560	3
NMU	physical association	0.560	3
PTTG1IP	physical association	0.560	3
RFFL	physical association	0.560	3

BioGRID (19 interactions; top human partners by supporting records): CAV1 (Affinity Capture-Western; 2 records), CAV2 (Affinity Capture-Western; 2 records), NCL (Protein-RNA; 2 records), PTGS2 (Affinity Capture-Western; 2 records), E2F4 (Affinity Capture-MS), EEA1 (Cross-Linking-MS (XL-MS)), FBXO6 (Affinity Capture-MS), IMMP1L (Proximity Label-MS), KIAA1429 (Affinity Capture-MS), PARP9 (Proximity Label-MS), PTGIS (FRET), RNF123 (Affinity Capture-MS), SFTPC (Affinity Capture-MS), TGOLN2 (Proximity Label-MS)

SIGNOR signaling

showing 11 of 12 signaling 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”

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ COX1 complex	1	PTGS1

Disease & clinical

Genetic variants

Variant evidence for PTGS1: 94 ClinVar records (0 pathogenic / likely pathogenic); 5 PharmGKB clinical annotations; 2 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 959):

Position(s)	Effect	Δscore	Sites
9:122381662–122381663	acceptor_loss	1.0000	6
9:122381748–122381749	donor_loss	1.0000	5
9:122383756–122383757	donor_loss	1.0000	5
9:122386733–122386734	donor_loss	1.0000	6
9:122371273–122371274	donor_loss	0.9900	5
9:122377309	acceptor_gain	0.9900
9:122378773–122378774	acceptor_loss	0.9900	6
9:122381478	acceptor_gain	0.9900
9:122381553–122381554	donor_loss	0.9900	5
9:122381703	donor_gain	0.9900

AlphaMissense

1,270 missense substitutions predicted likely pathogenic (of 3,949 scored), across 325 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F380	8	0.982	0.999
H206	8	0.972	0.991
F209	8	0.972	0.992
F204	8	0.954	0.992
H308	8	0.953	0.988
H387	8	0.952	0.991
F549	8	0.920	0.979
F197	8	0.895	0.959
D228	8	0.893	0.957
H203	8	0.891	0.987
H385	8	0.862	0.983
F579	8	0.859	0.958
H225	8	0.856	0.956
F517	8	0.783	0.903
F328	7	0.983	0.991
C46	7	0.982	0.991
C68	7	0.982	0.993
W386	7	0.981	0.998
C56	7	0.975	0.993
C58	7	0.974	0.986

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Ovary Serous Cystadenocarcinoma)

Disease associations

OMIM: gene MIM:176805 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

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

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
platelet-type bleeding disorder 12	Limited	SD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Bleeding and platelet disorders	green

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

GWAS associations

2 associations:

Study	Trait	p-value
GCST010396_149	Gut microbiota (bacterial taxa, hurdle binary method)	1e-6
GCST003139_21	Glomerular filtration rate in chronic kidney disease	4e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors

1 disease descriptors:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PTGS1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
ALCLOFENAC	Small molecule	4
MOFEZOLAC	Small molecule	4
ANTIPYRINE	Small molecule	3

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes PTGS1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

49 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ACEMETACIN	Cyclooxygenase	2	4
ACETAMINOPHEN	Cyclooxygenase	2	4
ASPIRIN	Cyclooxygenase	2	4
BALSALAZIDE DISODIUM	Cyclooxygenase	2	4
BENZYDAMINE	Cyclooxygenase	2	4
BISMUTH SUBSALICYLATE	Cyclooxygenase	2	4
BROMFENAC SODIUM	Cyclooxygenase	2	4
CLOMETACIN	Cyclooxygenase	2	4
DEXIBUPROFEN	Cyclooxygenase	2	4
DEXKETOPROFEN	Cyclooxygenase	2	4
DICLOFENAC	Cyclooxygenase	2	4
DICLOFENAC EPOLAMINE	Cyclooxygenase	2	4
DIFLUNISAL	Cyclooxygenase	2	4
DIPYRONE	Cyclooxygenase	2	4
ESFLURBIPROFEN	Cyclooxygenase	2	4
FENCLOFENAC	Cyclooxygenase	2	4
FENOPROFEN CALCIUM	Cyclooxygenase	2	4
FLURBIPROFEN	Cyclooxygenase	2	4
GLAFENINE	Cyclooxygenase	2	4
IBUFENAC	Cyclooxygenase	2	4
IBUPROFEN	Cyclooxygenase	2	4
IBUPROFEN LYSINE	Cyclooxygenase	2	4
INDOMETHACIN	Cyclooxygenase	2	4
INDOPROFEN	Cyclooxygenase	2	4
ISOXICAM	Cyclooxygenase	2	4
KETOPROFEN	Cyclooxygenase	2	4
KETOROLAC TROMETHAMINE	Cyclooxygenase	2	4
LOXOPROFEN	Cyclooxygenase	2	4
MECLOFENAMATE SODIUM	Cyclooxygenase	2	4
MEFENAMIC ACID	Cyclooxygenase	2	4
MESALAMINE	Cyclooxygenase	2	4
NAPROXEN	Cyclooxygenase	2	4
NEPAFENAC	Cyclooxygenase	2	4
OLSALAZINE SODIUM	Cyclooxygenase	2	4
OXAPROZIN	Cyclooxygenase	2	4
OXYPHENBUTAZONE	Cyclooxygenase	2	4
PHENYLBUTAZONE	Cyclooxygenase	2	4
PIROXICAM	Cyclooxygenase	2	4
PIRPROFEN	Cyclooxygenase	2	4
SULFASALAZINE	Cyclooxygenase	2	4
SULINDAC	Cyclooxygenase	2	4
SUPROFEN	Cyclooxygenase	2	4
TOLMETIN SODIUM	Cyclooxygenase	2	4
LORNOXICAM	Cyclooxygenase	2	3
NAPROXCINOD	Cyclooxygenase	2	3
ALOXIPRIN	Cyclooxygenase	2	2
APAZONE	Cyclooxygenase	2	2
NAPROXEN ETEMESIL	Cyclooxygenase	2	2
DICLOFENAC ETALHYALURONATE SODIUM	Cyclooxygenase	2	—

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,096,485 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 272 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL259972	MOFEZOLAC	4	3,971
CHEMBL1098319	2-MERCAPTOETHANESULFONIC ACID	4	6,528
CHEMBL291338	3,3’,4’,5-TETRACHLOROSALICYLANILIDE	4	727
CHEMBL404271	ACARBOSE	4	16
CHEMBL189171	ACEMETACIN	4	17,104
CHEMBL734	ACETOHYDROXAMIC ACID	4	7,130
CHEMBL705	ALITRETINOIN	4	39,748
CHEMBL530	AMDINOCILLIN	4	4,204
CHEMBL1112	ARIPIPRAZOLE	4	24,497
CHEMBL196	ASCORBIC ACID	4	1,043,187
CHEMBL25	ASPIRIN	4	696,632
CHEMBL2103883	AVATROMBOPAG	4	286
CHEMBL408513	BELINOSTAT	4	8,184
CHEMBL487253	BENDAMUSTINE	4	31,460
CHEMBL232201	BENZIODARONE	4	1,346
CHEMBL1293	BETA CAROTENE	4	95,169
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL1077	BROMFENAC	4	12,620
CHEMBL493	BROMOCRIPTINE	4	44,193
CHEMBL294199	CAPSAICIN	4	53,495
CHEMBL1560	CAPTOPRIL	4
CHEMBL46917	CARBARIL	4
CHEMBL1316	CARPROFEN	4
CHEMBL1630575	CASPOFUNGIN	4
CHEMBL1201016	CEFPODOXIME PROXETIL	4
CHEMBL118	CELECOXIB	4
CHEMBL1200971	CEPHALOGLYCIN	4
CHEMBL316157	CEPHALORIDINE	4
CHEMBL908	CHLORPROTHIXENE	4
CHEMBL1042	CHOLECALCIFEROL	4
CHEMBL311498	CIANIDANOL	4
CHEMBL2355051	CLOMIPHENE	4
CHEMBL6067481	COLISTIN	4
CHEMBL771	CYCLOSERINE	4
CHEMBL863	CYSTEINE	4
CHEMBL1554	DACTINOMYCIN	4
CHEMBL218650	DELAMANID	4
CHEMBL333826	DEQUALINIUM	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1429	DESMOPRESSIN	4
CHEMBL1533	DESOGESTREL	4
CHEMBL175	DEXIBUPROFEN	4
CHEMBL75435	DEXKETOPROFEN	4
CHEMBL1200979	DEXPANTHENOL	4
CHEMBL1738	DEXRAZOXANE	4
CHEMBL139	DICLOFENAC	4
CHEMBL1034	DICLOFENAC SODIUM	4
CHEMBL411	DIETHYLSTILBESTROL	4
CHEMBL1237072	DIRITHROMYCIN	4
CHEMBL59	DOPAMINE	4
CHEMBL53463	DOXORUBICIN	4
CHEMBL2103827	DROXIDOPA	4
CHEMBL290916	EDARAVONE	4
CHEMBL2110588	ELIGLUSTAT	4
CHEMBL3989908	ENASIDENIB	4
CHEMBL417	EPIRUBICIN	4
CHEMBL1536	ERGOCALCIFEROL	4
CHEMBL553	ERLOTINIB	4
CHEMBL1359	ERTAPENEM	4
CHEMBL435298	ESFLURBIPROFEN	4

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

5 annotations by evidence level (1 strongest → 4):

Variant	Association	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

3 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10306114	PTGS1	3	6.00	3	aspirin;clopidogrel;aspirin;latanoprost
rs10306135	PTGS1	3	3.25	1	Antiinflammatory agents;non-steroids
rs1330344	PTGS1	3	2.25	1	clopidogrel

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

10 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs5789	Antiinflammatory agents, non-steroids	Toxicity	Allele C is associated with decreased likelihood of aspirin-induced asthma when exposed to Antiinflammatory agents, non-steroids in people with Asthma as compared to allele A.	PMID:26067486
rs10306135	Antiinflammatory agents, non-steroids	Toxicity	Allele A is associated with increased likelihood of aspirin-induced asthma when exposed to Antiinflammatory agents, non-steroids in people with Asthma as compared to allele T.	PMID:26067486
rs1330344	clopidogrel	Efficacy	Allele T is associated with increased risk of major adverse cardiac events (mace) when treated with clopidogrel as compared to allele C.	PMID:26870959
rs10306114	aspirin	Efficacy	Genotypes AA + AG is associated with increased likelihood of Recurrence when treated with aspirin in people with Cerebral Infarction as compared to genotype GG.	PMID:38728491
rs3842787	celecoxib	Efficacy	Allele T is associated with reduction in COX-1 inhibition when exposed to celecoxib in healthy individuals as compared to allele C.	PMID:16401468
rs3842787	rofecoxib	Efficacy	Allele T is associated with reduction in COX-1 inhibition and depression of the urinary thromboxane metabolite when exposed to rofecoxib in healthy individuals as compared to allele C.	PMID:16401468
rs10306135	Antiinflammatory agents, non-steroids	Toxicity	Genotype TT is associated with increased likelihood of Acute coronary syndrome when exposed to Antiinflammatory agents, non-steroids in people with Acute coronary syndrome as compared to genotypes AA + AT.	PMID:20538124
rs12353214	Antiinflammatory agents, non-steroids	Toxicity	Genotype TT is associated with increased likelihood of Acute coronary syndrome when exposed to Antiinflammatory agents, non-steroids in people with Acute coronary syndrome as compared to genotypes CC + CT.	PMID:20538124
rs10306114	aspirin, clopidogrel	Toxicity	Genotypes AG + GG are associated with increased risk of cardiovascular events when treated with aspirin and clopidogrel in people with ST-segment elevation myocardial infarction (STEMI) as compared to genotype AA.	PMID:22940005
rs10306114	aspirin	Efficacy	Allele G is associated with increased risk of non-response to aspirin when treated with aspirin in people with Coronary Artery Disease as compared to genotype AA.	PMID:16493486

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)

1812 measured of 2869 human assays (3006 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL1922655	IC50	0.4 nM
CHEMBL1922663	IC50	0.4 nM
CHEMBL1922532	IC50	0.5 nM
CHEMBL1922661	IC50	0.6 nM
CHEMBL1922664	IC50	0.6 nM
CHEMBL1922666	IC50	0.6 nM
CHEMBL1229205	IC50	0.6 nM
CHEMBL4476621	IC50	0.6 nM
CHEMBL1922660	IC50	0.7 nM
3,5-Bis-(4-fluoro-phenyl)-4-aza-tricyclo[5.2.1.0*2,6*]deca-2,5-diene	IC50	1 nM
CHEMBL5206077	IC50	1 nM
CHEMBL1945285	IC50	1.2 nM
CHEMBL259972	IC50	1.4 nM
2-(4-Fluoro-phenyl)-4-(3-methoxy-benzyloxy)-3-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-6-ylamine	IC50	1.5 nM
L-689037	IC50	2 nM
sodium 3-(3-(tert-butylthio)-1-(4-(5-methoxypyrimidin-2-yl)benzyl)-5-((5-methylpyridin-2-yl)methoxy)-1H-indol-2-yl)-2,2-dimethylpropanoate	IC50	2 nM
(2R)-6,8-dichloro-7-(2-methylpropoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid	IC50	2 nM
Pf-06273340	IC50	4 nM
CHEMBL5184826	IC50	4 nM
CHEMBL3427203	IC50	4.9 nM
(2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine	KI	5 nM
4-[6-(4-Methoxy-phenyl)-spiro[2.4]hept-5-en-5-yl]-benzenesulfonamide	IC50	5 nM
1,5-Bis-(4-methoxy-phenyl)-3-trifluoromethyl-1H-pyrazole	IC50	5 nM
3-(3-(tert-butylthio)-1-(3-(6-methoxypyridin-3-yl)benzyl)-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid	IC50	5.5 nM
4-[3-(4-Fluoro-phenyl)-1H-inden-2-yl]-benzenesulfonamide	IC50	7 nM
2-(3-(7-chloroquinolin-4-yl)-2,5-dimethyl-1H-indol-1-yl)acetic acid	IC50	8 nM
5-Bromo-2-(4-fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-thiophene	IC50	10 nM
4-[2-Benzylamino-4-(3-fluoro-4-methoxy-phenyl)-thiazol-5-yl]-benzenesulfonamide	IC50	10 nM
Indometacin	IC50	10 nM
Acemetacin	IC50	10 nM
CHEMBL2023649	IC50	13 nM
(5-(3-amino-3-methylbut-1-ynyl)-2-methoxyphenyl)(4-(2,4-difluorophenylamino)phenyl)methanone	IC50	14 nM
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide	KI	16 nM
CHEMBL2235865	KD	16 nM
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methylindol-2-yl]propanoic acid	IC50	17.7 nM	US-9346803: Indomethacin analogs for the treatment of castrate-resistant prostate cancer
1-(4-Chloro-phenyl)-5-(4-methoxy-phenyl)-3-trifluoromethyl-1H-pyrazole	IC50	18 nM
CHEMBL2037483	IC50	20 nM
3,4-Dihydroxycinnamate, XVII	IC50	24 nM
FR-122047	IC50	28 nM
4-(4-(2-(Pyrrolidin-1-yl)ethoxy)phenoxy)aniline	IC50	29 nM
1-[2-(4-Phenoxy-phenoxy)-ethyl]-pyrrolidine	IC50	30 nM
3,5-Bis-(4-fluoro-phenyl)-4-aza-tricyclo[5.2.2.0*2,6*]undeca-2,5-diene	IC50	30 nM
CHEMBL5279593	IC50	30 nM
CHEMBL5271431	IC50	30 nM
(7-tert-Butyl-3,3-dimethyl-2,3-dihydro-benzofuran-5-yl)-(1-methyl-1H-pyrrol-2-yl)-methanone	IC50	35 nM
CHEMBL4067927	IC50	36 nM
CHEMBL4083642	IC50	40 nM
1-(2-(4-(4-Chlorophenoxy)phenoxy)ethyl)pyrrolidine	IC50	40 nM
CHEMBL4860329	IC50	40 nM
CHEMBL5268642	IC50	40 nM

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

1009 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
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
(3E)-3-[(7-tert-butyl-3,3-dimethyl-2H-1-benzofuran-5-yl)methylidene]oxolan-2-one	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 expression, decreases chemical synthesis, decreases response to substance, increases expression, affects response to substance (+6 more)	10
Indomethacin	increases chemical synthesis, decreases expression, increases expression, affects cotreatment, decreases activity (+2 more)	8
Tretinoin	decreases reaction, increases expression, decreases expression	6
SC 560	decreases reaction, increases activity, decreases activity	4
Resveratrol	decreases reaction, increases activity, decreases activity, decreases expression	4
Acetaminophen	decreases activity, decreases expression	4
Estradiol	affects cotreatment, increases expression, affects expression	4
Arachidonic Acid	decreases reaction, increases chemical synthesis, increases metabolic processing, increases activity, increases response to substance (+1 more)	4
bisphenol A	affects expression, decreases expression, affects cotreatment	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	increases expression, affects response to substance, affects expression	3
Dexamethasone	decreases reaction, increases expression, affects cotreatment, decreases expression	3
Ethinyl Estradiol	affects expression, decreases expression	3
Ibuprofen	decreases activity	3
Lipopolysaccharides	decreases reaction, increases expression, decreases expression, affects cotreatment	3
Progesterone	increases expression, affects cotreatment	3
Dinoprostone	increases reaction, decreases reaction, increases chemical synthesis, increases abundance	3
mercuric bromide	affects cotreatment, decreases expression	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 reaction, increases expression, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Calcitriol	increases expression	2
Diclofenac	decreases activity, decreases expression, affects cotreatment	2
Diethylhexyl Phthalate	decreases expression, affects cotreatment, affects expression, affects reaction	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PTGS1 across ~30M SureChEMBL compounds — explore on Sugi Predict.