PTGS2

Summary

PTGS2 (prostaglandin-endoperoxide synthase 2, HGNC:9605) is a protein-coding gene on chromosome 1q31.1, encoding Prostaglandin G/H synthase 2 (P35354). Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response.

Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis.

Source: NCBI Gene 5743 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 56 total
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 16 curated mechanism-of-action drugs, 49 via a complex or family; 192 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 10 — Carprofen, Celecoxib, Etodolac, +7 more
• Approved drugs acting on a complex or family including it: 43 — Acemetacin, Acetaminophen, Aspirin, +40 more (Cyclooxygenase)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.33 (highly constrained)
• MANE Select transcript: NM_000963
• Interaction hub: 4,954 STRING partners (top 1% of genes corpus-wide)
• Notable: 56 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9605
Approved symbol	PTGS2
Name	prostaglandin-endoperoxide synthase 2
Location	1q31.1
Locus type	gene with protein product
Status	Approved
Aliases	COX2
Ensembl gene	ENSG00000073756
Ensembl biotype	protein_coding
OMIM	600262
Entrez	5743

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 2 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000367468

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1

ENST00000367468, ENST00000466691, ENST00000490885, ENST00000559627, ENST00000680451, ENST00000681605

RefSeq mRNA: 1 — MANE Select: NM_000963 NM_000963

CCDS: CCDS1371

Canonical transcript exons

ENST00000367468 — 10 exons

Exon	Start	End
ENSE00002401108	186671791	186674762
ENSE00002570587	186680239	186680423
ENSE00003548045	186679322	186679438
ENSE00003548799	186677649	186677830
ENSE00003551831	186676833	186676916
ENSE00003563132	186679058	186679201
ENSE00003576370	186676467	186676713
ENSE00003652822	186675898	186676184
ENSE00003655093	186675249	186675396
ENSE00003667680	186678261	186678404

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 106.5173 / max 22952.2141, expressed in 1134 samples.

Highest expression (Bgee): seminal vesicle, cartilage tissue, mucosa of urinary bladder, type B pancreatic cell, periodontal ligament.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PTGS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.3e-03	-0.31	1:186680089:A:G
Nerve Tibial	eqtl	4.8e-03	-0.23	1:186141451:T:C
Brain Hippocampus	eqtl	1.2e-02	-0.43	1:186871978:T:C
Spleen	eqtl	3.8e-02	+0.93	1:185719785:T:C
Skin Sun Exposed Lower leg	eqtl	4.2e-02	-0.43	1:186856785:G:C
Brain Cerebellum	eqtl	4.2e-02	-0.33	1:186229939:C:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
16368	106.2792	1134
16367	0.2381	88

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.59	gold quality
cartilage tissue	UBERON:0002418	99.27	gold quality
mucosa of urinary bladder	UBERON:0001259	98.91	gold quality
type B pancreatic cell	CL:0000169	98.50	gold quality
periodontal ligament	UBERON:0008266	98.37	gold quality
vena cava	UBERON:0004087	98.16	gold quality
visceral pleura	UBERON:0002401	94.17	gold quality
saphenous vein	UBERON:0007318	94.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.99	gold quality
gall bladder	UBERON:0002110	93.64	gold quality
mucosa of stomach	UBERON:0001199	92.57	gold quality
pleura	UBERON:0000977	91.17	gold quality
monocyte	CL:0000576	90.60	gold quality
bone marrow cell	CL:0002092	90.48	gold quality
mononuclear cell	CL:0000842	90.24	gold quality
leukocyte	CL:0000738	90.07	gold quality
lower lobe of lung	UBERON:0008949	89.75	gold quality
parietal pleura	UBERON:0002400	89.19	gold quality
bone marrow	UBERON:0002371	88.25	gold quality
islet of Langerhans	UBERON:0000006	87.74	gold quality
urethra	UBERON:0000057	87.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.08	gold quality
smooth muscle tissue	UBERON:0001135	86.09	gold quality
urinary bladder	UBERON:0001255	85.59	gold quality
lung	UBERON:0002048	85.59	gold quality
choroid plexus epithelium	UBERON:0003911	84.78	gold quality
epithelial cell of pancreas	CL:0000083	84.34	gold quality
upper lobe of lung	UBERON:0008948	84.23	gold quality
upper lobe of left lung	UBERON:0008952	84.01	gold quality
prostate gland	UBERON:0002367	83.58	gold quality
rectum	UBERON:0001052	83.11	gold quality
vermiform appendix	UBERON:0001154	82.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.48	gold quality
colonic epithelium	UBERON:0000397	81.81	gold quality
blood	UBERON:0000178	81.75	gold quality
granulocyte	CL:0000094	81.71	gold quality
cauda epididymis	UBERON:0004360	80.58	gold quality
sigmoid colon	UBERON:0001159	80.47	gold quality
nasal cavity epithelium	UBERON:0005384	79.67	gold quality
caecum	UBERON:0001153	78.83	gold quality
oviduct epithelium	UBERON:0004804	78.40	gold quality
lymph node	UBERON:0000029	78.18	gold quality
upper leg skin	UBERON:0004262	78.10	gold quality
left uterine tube	UBERON:0001303	77.79	gold quality
cardiac atrium	UBERON:0002081	77.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.58	gold quality
mammary duct	UBERON:0001765	77.49	gold quality
epithelium of mammary gland	UBERON:0003244	77.44	gold quality
right atrium auricular region	UBERON:0006631	77.36	gold quality
metanephros cortex	UBERON:0010533	77.25	gold quality
omental fat pad	UBERON:0010414	77.21	gold quality
peritoneum	UBERON:0002358	77.15	gold quality
sperm	CL:0000019	76.99	gold quality
fallopian tube	UBERON:0003889	76.68	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.66	gold quality
right lung	UBERON:0002167	76.57	gold quality
nasal cavity mucosa	UBERON:0001826	76.43	gold quality
tibial artery	UBERON:0007610	76.10	gold quality
popliteal artery	UBERON:0002250	76.01	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.58	gold quality
blood vessel layer	UBERON:0004797	75.37	gold quality
aorta	UBERON:0000947	75.33	gold quality
ascending aorta	UBERON:0001496	74.98	gold quality
male germ cell	CL:0000015	74.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.43	gold quality
thoracic aorta	UBERON:0001515	74.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.97	gold quality
coronary artery	UBERON:0001621	73.60	gold quality
spinal cord	UBERON:0002240	73.60	gold quality
large intestine	UBERON:0000059	73.51	gold quality
left coronary artery	UBERON:0001626	73.49	gold quality
colon	UBERON:0001155	73.04	gold quality
palpebral conjunctiva	UBERON:0001812	73.04	gold quality
right coronary artery	UBERON:0001625	72.67	gold quality
trachea	UBERON:0003126	72.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	72.03	gold quality
cervix epithelium	UBERON:0004801	71.91	gold quality
cardia of stomach	UBERON:0001162	71.73	gold quality
adult organism	UBERON:0007023	71.42	gold quality
primary visual cortex	UBERON:0002436	71.31	gold quality
lower esophagus	UBERON:0013473	71.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.16	gold quality
lower esophagus mucosa	UBERON:0035834	71.04	gold quality
intestine	UBERON:0000160	70.87	gold quality
epithelium of nasopharynx	UBERON:0001951	70.86	gold quality
superficial temporal artery	UBERON:0001614	70.84	gold quality
fundus of stomach	UBERON:0001160	70.01	gold quality
caput epididymis	UBERON:0004358	69.81	gold quality
penis	UBERON:0000989	69.60	gold quality
germinal epithelium of ovary	UBERON:0001304	69.52	gold quality
adenohypophysis	UBERON:0002196	69.47	gold quality
descending thoracic aorta	UBERON:0002345	69.37	gold quality
prefrontal cortex	UBERON:0000451	69.29	gold quality
stomach	UBERON:0000945	68.91	gold quality
right lobe of liver	UBERON:0001114	68.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.83	gold quality
layer of synovial tissue	UBERON:0007616	68.43	gold quality
mammary gland	UBERON:0001911	68.37	gold quality
thoracic mammary gland	UBERON:0005200	68.33	gold quality
body of stomach	UBERON:0001161	68.06	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	828.28
E-MTAB-8559	yes	347.14
E-CURD-46	yes	21.07
E-GEOD-135922	yes	6.43
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Urinary bladder	tissue	151.3	high
Seminal vesicle	tissue	120.2	high
Bone marrow	tissue	110.4	low
Cervix	tissue	58.4	low
Gallbladder	tissue	29.6	high
Prostate	tissue	23.4	low
Hippocampal formation	tissue	21.8
Entorhinal cortex	tissue	21.8
Prefrontal cortex	tissue	21.2
Cerebral cortex	tissue	21.2	not detected
Occipital cortex	tissue	20.4
Lung	tissue	18.6	low
Insular cortex	tissue	18.5
Retrosplenial and cingulate cortex	tissue	18.1
Temporal cortex	tissue	17.9
Retrosplenial cortex	tissue	17.4
Adipose tissue	tissue	15.9	not detected
Motor cortex	tissue	15.8
Somatosensory cortex	tissue	14.8
Appendix	tissue	13.1	high
Smooth muscle	tissue	11.4	not detected
Rectum	tissue	9.3	high
Lymph node	tissue	8.3	not detected
Endometrium 1	tissue	8.3	low
Placenta	tissue	7.9	not detected
Adrenal gland	tissue	7.5	not detected
Liver	tissue	7.4	not detected
Spinal cord	tissue	7.4
Esophagus	tissue	6.5	not detected
Frontal cortex	tissue	6.5
Tongue	tissue	6.0
Kidney	tissue	5.5	not detected
Parathyroid gland	tissue	5.2
Thymus	tissue	4.9
Fallopian tube	tissue	4.8	low
Amygdala	tissue	4.4
Choroid plexus	tissue	3.9
Colon	tissue	3.4
Superior colliculi	tissue	3.1
Thyroid gland	tissue	3.0	not detected
Olfactory bulb	tissue	2.9
Pituitary gland	tissue	2.8
Breast	tissue	2.8
Heart muscle	tissue	2.8	not detected
Small intestine	tissue	2.8	high
Spleen	tissue	2.7	not detected
Substantia nigra	tissue	2.4
Duodenum	tissue	2.4	high
Stomach 1	tissue	2.2	not detected
Midbrain	tissue	2.2
Vagina	tissue	2.1	not detected
Pancreas	tissue	2.1	not detected
Septum	tissue	2.0
Pons	tissue	1.8
Medulla oblongata	tissue	1.8
Thalamus	tissue	1.8
Ventral forebrain	tissue	1.8
Basal ganglia	tissue	1.7	not detected
Ovary	tissue	1.6	not detected
Corpus callosum	tissue	1.6

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Subiculum (8.9), Blood vessel (8.1), Dorsal spinal cord (7.4), Temporo-occipital transitional zone (6.4), Dorsal hippocampus (5.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, APC, AR, ARID4B, ARNT, ATF1, ATF2, ATF4, ATP2B4, CDX1, CDX2, CEBPA, CEBPB, CEBPD, CEBPG, CREB1, CREBBP, CTNNB1, DDIT3, DNMT1, DNMT3B, DR1, E2F1, E2F4, EGR1, EGR2, ELF3, ELK1, ENO1, EP300, ESR1, ETS1, ETV4, ETV5, EZH2, FOS, FOXC1, FOXL2, FOXM1

miRNA regulators (miRDB)

Targeting PTGS2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 131 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.33, missense Z 3.09 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000367468 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:186,674,356–186,676,004	219 / 267.4	0.82	no
1:186,676,005–186,676,665	67 / 152.6	0.44	no
1:186,676,666–186,678,281	118 / 138.7	0.85	no
1:186,678,282–186,678,372	11 / 35.2	0.31	yes (p 4.6e-05)
1:186,678,373–186,680,290	118 / 144.6	0.82	no

Literature-anchored findings (GeneRIF, showing 40)

• Increased expression of iNOS and production of prostanoids in colon cancer parallels the increase in COX-2, confirming the importance of this enzyme in colon cancer. (PMID:11705852)
• Findings collectively suggest the possibility that COX-2 is mainly produced in follicles in a preovulatory phase, while after ovulation, COX-2 is produced in interstitial cells in human ovary. (PMID:11712072)
• 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)
• induction in monocytes by peroxisome proliferator activated receptor gamma and oxidized alkyl phospholipids from oxidized low density lipoprotein (PMID:11809750)
• increased expression associated with chemotherapy resistance and poor survival in cervical cancer (PMID:11844819)
• Up-regulation of prostaglandin E2 synthesis by interleukin-1beta in human orbital fibroblasts involves coordinate induction of prostaglandin-endoperoxide H synthase-2 and glutathione-dependent prostaglandin E2 synthase expression (PMID:11847219)
• Aromatase and COX-2 expression in human breast cancers. (PMID:11850206)
• Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication (PMID:11867761)
• in intestinal myofibroblasts, IL-1-mediated induction of COX-2 expression is a complex process that requires input from multiple signaling pathways. (PMID:11880271)
• COX-2 is an independent prognostic factor for poor survival (relative risk, 2.74; 95% CI, 1.38 to 5.47) in ovarian carcinoma. (PMID:11891188)
• co-stimulatory mechanisms may exist that increase the expression of cox-2 and laminin-5 at the invasive front of lung adenocarcinomas and that EGFR signaling could be one of the mechanisms (PMID:11891209)
• 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)
• overexpresssion in HER-2 positive breast cancer with involvement of AP-1 and PEA3 (PMID:11901151)
• 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors (PMID:11906292)
• Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors (PMID:11911965)
• Reduced prostate cancer growth after exposure to saw palmetto extract may relate to decreased expression of Cox-2 (PMID:11913955)
• greater expression seen in adenocarcinoma rather than squamous cell carcinoma of lung; no correlation seen between increased expression and major clinicopathologic factors (PMID:11920472)
• highly expressed in adenoma and adenocarcinoma in intraductal papillary-mucinous tumors of the pancreas (PMID:11920515)
• overexpression of COX-2 and iNOS were revealed in epithelial cells of lymphocytic thyroiditis and thyroid tumors (PMID:11939728)
• In advanced gallbladder carcinoma, enhanced expression of cyclooxygenase-2 is observed in the adjacent stroma. (PMID:11948128)
• COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP (PMID:11957147)
• Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells (PMID:11959891)
• Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu are expressed in ovarian cancer. (PMID:11972392)
• COX-2 appears to be constitutively and selectively present in medullary epithelial cells of the human thymus. (PMID:11981837)
• The MEK/ERK pathway mediates COX-2-selective NSAID-induced apoptosis and induced COX-2 protein expression in colorectal carcinoma cells (PMID:11992399)
• Serous cystadenocarcinomas also had an unexpectedly high expression of COX-2. (PMID:11994539)
• malignant endometrial epithelial cells secrete PGE(2) that induces COX-2 expression in normal endometrial stromal cells in a paracrine fashion through activation of transcription and stabilization of COX-2 mRNA (PMID:12006564)
• induction of promoter activity by deoxycholic acid (PMID:12016158)
• results suggest that NFkappaB is involved in the IL-1beta-induced COX-2 expression in the mesenchymal cells of human amnion (PMID:12021045)
• expression is induced during human megekaryopoiesis and characterizes newly formed platelets (PMID:12032335)
• expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells (PMID:12050157)
• cyclooxygenase gene expression in human preimplantation embryos. (PMID:12050227)
• data collectively imply COX-2 may play an important role during premalignant hyperproliferation, as well as the later stages of invasive carcinoma and metastasis in various human epithelial cancers (PMID:12051953)
• Cholesterol-sensitive transcriptional pathways that regulate COX-2 expression are present in vascular tissue. (PMID:12067908)
• Cox-2 could participate in the carcinogenic process of oral mucosa (PMID:12070598)
• PI3K destabilizes cyclooxygenase 2 mRNA (PMID:12072439)
• increased expression associated with development of lung cancer and possibly acquisition of invasive/metastatis phenotype (PMID:12086404)
• Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer. (PMID:12124799)
• COX-2 may be involved in inflammatory responses in chronic pancreatitis and in the progression of this chronic inflammatory disease. (PMID:12131767)
• ERBB-2 overexpression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions. (PMID:12143054)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptgs2a	ENSDARG00000004539
danio_rerio	ptgs2b	ENSDARG00000010276
mus_musculus	Ptgs2	ENSMUSG00000032487
rattus_norvegicus	Ptgs2	ENSRNOG00000002525

Paralogs (1): PTGS1 (ENSG00000095303)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97798) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 189 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased prostaglandin level	9
abnormal renal glomerulus morphology	6
premature death	5
increased blood urea nitrogen level	5
abnormal kidney cortex morphology	4
pale kidney	4
glomerulosclerosis	4
renal glomerulus hypertrophy	4
abnormal kidney development	3
female infertility	3
abnormal kidney morphology	3
small kidney	3
renal interstitial fibrosis	3
peritoneal inflammation	3
increased circulating creatinine level	3
increased susceptibility to xenobiotic induced morbidity/mortality	3
decreased superovulation rate	3
decreased hematocrit	2
alopecia	2
sparse hair	2
weight loss	2
reduced female fertility	2
abnormal renal tubule morphology	2
dilated renal tubule	2
abnormal nociception after inflammation	2

+164 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
PDC-AS1	ncRNA	102724919
PACERR	ncRNA	103752588
PDC	protein-coding	5132
ODR4	protein-coding	54953
PRG4	protein-coding	10216
TPR	protein-coding	7175
LINC01036	ncRNA	104169671
PLA2G4A	protein-coding	5321
LINC01037	ncRNA	106144535

Protein

Protein identifiers

Prostaglandin G/H synthase 2 — P35354 (reviewed: P35354)

Alternative names: Cyclooxygenase-2, PHS II, Prostaglandin H2 synthase 2, Prostaglandin-endoperoxide synthase 2

All UniProt accessions (3): A0A7P0T828, P35354, Q6ZYK7

UniProt curated annotations — full annotation on UniProt →

Function. Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. 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. Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins. In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids. Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response. Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols. Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection. In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE). 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. During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia.

Subunit / interactions. Homodimer.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane. Nucleus inner membrane. Nucleus outer membrane.

Post-translational modifications. S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526. Acetylated at Ser-565 by SPHK1. During neuroinflammation, acetylation by SPHK1 promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.

Activity regulation. The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, flurbiprofen, celecoxib, flufenamic, mefenamic and tolfenamic acids as well as by hydroperoxide scavenger erythrocyte glutathione peroxidase GPX1. Aspirin triggers enzyme acetylation turning off its ability to generate pro-inflammatory prostaglandins, but switches on its capacity to produce anti-inflammatory lipid mediators involved in inflammation resolution. Aspirin enhances lipoxygenase-type activity toward production of epimers with R stereochemistry such as 15R-HETE, 18R-HEPE, 15R-HEPE and 17R-HDHA. Atorvastatin, a cholesterol-lowering drug, triggers enzyme S-nitrosylation increasing production of 13-series resolvins (RvTs).

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

Induction. By cytokines and mitogens. Up-regulated by IL1B. Up-regulated by lipopolysaccharide (LPS).

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.

RefSeq proteins (1): NP_000954* (*=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 + O2 = 11R-hydroperoxy-(5Z,8Z,12E,14Z)-eicosatetraenoate (RHEA:42280)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (RHEA:42284)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2 (RHEA:42596)
• prostaglandin G2 + AH2 = prostaglandin H2 + A + H2O (RHEA:42600)
• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + 2 O2 = 2-glyceryl-prostaglandin G2 (RHEA:45288)
• 2-glyceryl-prostaglandin G2 + AH2 = 2-glyceryl-prostaglandin H2 + A + H2O (RHEA:45292)
• (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,11R)-dihydroxy-(6E,8Z,12E,14Z)-eicosatetraenoate + A + H2O (RHEA:48804)
• (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O (RHEA:48808)
• (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,15R)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2O (RHEA:48812)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 17R-hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + A + H2O (RHEA:48816)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 13-hydroxy-(4Z,7Z,10Z,14E,16Z,19Z)-docosahexaenoate + A + H2O (RHEA:48820)

UniProt features (98 total): helix 39, strand 14, mutagenesis site 11, turn 7, disulfide bond 5, sequence variant 5, glycosylation site 4, binding site 3, modified residue 2, active site 2, sequence conflict 2, signal peptide 1, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
5F19	The Crystal Structure of Aspirin Acetylated Human Cyclooxygenase-2	X-RAY DIFFRACTION	2.04
5IKR	The Structure of Mefenamic Acid Bound to Human Cyclooxygenase-2	X-RAY DIFFRACTION	2.34
5F1A	The Crystal Structure of Salicylate Bound to Human Cyclooxygenase-2	X-RAY DIFFRACTION	2.38
5IKQ	The Structure of Meclofenamic Acid Bound to Human Cyclooxygenase-2	X-RAY DIFFRACTION	2.41
5IKT	The Structure of Tolfenamic Acid Bound to Human Cyclooxygenase-2	X-RAY DIFFRACTION	2.45
5IKV	The Structure of Flufenamic Acid Bound to Human Cyclooxygenase-2	X-RAY DIFFRACTION	2.51
5KIR	The Structure of Vioxx Bound to Human COX-2	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35354-F1	93.37	0.91

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; cytosol

Antibody reliability (HPA): IH enhanced · IF supported

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
193	proton acceptor
371	for cyclooxygenase activity
516	aspirin-acetylated serine

Ligand- & substrate-binding residues (3)

Position	Role
106	substrate
341	substrate
374	heme b

Post-translational modifications (2)

Type	Positions
O-acetylserine	565
S-nitrosocysteine	526

Disulfide bonds (5)

Type	Positions
Disulfide bond	21–32, 22–145, 26–42, 44–54, 555–561

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	53, 130, 396, 580

Mutagenesis-validated functional residues (11)

Position	Phenotype
189	increases two-electron hydroperoxide reduction. has no effect on cyclooxygenase activity.
189	impairs two-electron hydroperoxide reduction and cyclooxygenase activity.
189	impairs two-electron hydroperoxide reduction.
193	reduces two-electron hydroperoxide reduction and cyclooxygenase activity. catalyzes predominantly one-electron hydroperoxide reduction.
371	decreased protein stability. increased decrease of protein stability; when associated with a-516.
516	no effect on protein stability. increased decrease of protein stability; when associated with a-371.
516	decreased enzyme activity with arachidonic acid. loss of cyclooxygenase activity; when associated with v-519.
519	loss of cyclooxygenase activity. loss of cyclooxygenase activity; when associated with t-516.
526	prevents activation by nitric oxid (no).
555	abolishes enzyme activity.
561	does not affect activation by nitric oxid (no).

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-9018677	Biosynthesis of DHA-derived SPMs	curated
R-HSA-9025094	Biosynthesis of DPAn-3 SPMs	curated
R-HSA-9018679	Biosynthesis of EPA-derived SPMs	curated
R-HSA-9027604	Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives	curated
R-HSA-6783783	Interleukin-10 signaling	curated
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-2142770	Synthesis of 15-eicosatetraenoic acid derivatives	curated
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	curated
R-HSA-2142753	Arachidonate metabolism	—
R-HSA-9018683	Biosynthesis of DPA-derived SPMs	—
R-HSA-9018678	Biosynthesis of specialized proresolving mediators (SPMs)	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-8978868	Fatty acid metabolism	—
R-HSA-168256	Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 675 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, BROWNE_HCMV_INFECTION_4HR_UP, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, PID_S1P_S1P1_PATHWAY, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_BLOOD_PRESSURE, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, FISCHER_G1_S_CELL_CYCLE, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS

GO Biological Process (28): prostaglandin biosynthetic process (GO:0001516), response to oxidative stress (GO:0006979), regulation of blood pressure (GO:0008217), positive regulation of vascular endothelial growth factor production (GO:0010575), cyclooxygenase pathway (GO:0019371), lipoxygenase pathway (GO:0019372), positive regulation of prostaglandin biosynthetic process (GO:0031394), positive regulation of fever generation (GO:0031622), long-chain fatty acid biosynthetic process (GO:0042759), positive regulation of nitric oxide biosynthetic process (GO:0045429), regulation of inflammatory response (GO:0050727), brown fat cell differentiation (GO:0050873), cellular response to hypoxia (GO:0071456), cellular response to non-ionic osmotic stress (GO:0071471), positive regulation of transforming growth factor beta production (GO:0071636), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), positive regulation of fibroblast growth factor production (GO:0090271), positive regulation of brown fat cell differentiation (GO:0090336), positive regulation of platelet-derived growth factor production (GO:0090362), regulation of neuroinflammatory response (GO:0150077), negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress (GO:1902219), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), prostaglandin metabolic process (GO:0006693), negative regulation of apoptotic process (GO:0043066), prostanoid biosynthetic process (GO:0046457), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (12): peroxidase activity (GO:0004601), prostaglandin-endoperoxide synthase activity (GO:0004666), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen (GO:0016701), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), enzyme binding (GO:0019899), heme binding (GO:0020037), protein homodimerization activity (GO:0042803), 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): nuclear inner membrane (GO:0005637), nuclear outer membrane (GO:0005640), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), neuron projection (GO:0043005)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Biosynthesis of specialized proresolving mediators (SPMs)	4
Arachidonate metabolism	2
Signaling by Interleukins	2
Metabolism of lipids	2
Biosynthesis of DPA-derived SPMs	1
Immune System	1
Fatty acid metabolism	1
Cytokine Signaling in Immune system	1
Metabolism	1

GO top-level categories

showing 60 of 73 GO namespaces:

Category	Terms
positive regulation of cytokine production	4
oxidoreductase activity	3
prostaglandin biosynthetic process	2
nuclear membrane	2
nuclear outer membrane-endoplasmic reticulum membrane network	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
response to stress	1
blood circulation	1
regulation of biological quality	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
arachidonate metabolic process	1
fatty acid metabolic process	1
icosanoid metabolic process	1
regulation of prostaglandin biosynthetic process	1
positive regulation of unsaturated fatty acid biosynthetic process	1
fever generation	1
positive regulation of acute inflammatory response	1
regulation of fever generation	1
positive regulation of heat generation	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
nitric oxide biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of nitric oxide biosynthetic process	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
fat cell differentiation	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
response to non-ionic osmotic stress	1
cellular response to osmotic stress	1
transforming growth factor beta production	1
regulation of transforming growth factor beta production	1
cell migration involved in sprouting angiogenesis	1
positive regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
fibroblast growth factor production	1
regulation of fibroblast growth factor production	1
positive regulation of fat cell differentiation	1
brown fat cell differentiation	1
regulation of brown fat cell differentiation	1
platelet-derived growth factor production	1
regulation of platelet-derived growth factor production	1
regulation of inflammatory response	1
neuroinflammatory response	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
protein binding	1
tetrapyrrole binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 47 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to hypoxia	BP	expression pattern
cyclooxygenase pathway	BP	direct assay
prostaglandin biosynthetic process	BP	direct assay
cytoplasm	CC	direct assay
endoplasmic reticulum	CC	direct assay
neuron projection	CC	direct assay
nuclear inner membrane	CC	direct assay
nuclear outer membrane	CC	direct assay
enzyme binding	MF	physical interaction
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	MF	experiment
prostaglandin-endoperoxide synthase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,954 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGS2	IL1B	P01584	930
PTGS2	IL6	P05231	928
PTGS2	TNF	P01375	910
PTGS2	NOS2	P35228	857
PTGS2	PTGER4	P35408	838
PTGS2	CXCL8	P10145	838
PTGS2	NFKBIA	P25963	834
PTGS2	PTGES	O14684	814
PTGS2	IFNG	P01579	804
PTGS2	NFKB1	P19838	803
PTGS2	IL10	P22301	780
PTGS2	MMP9	P14780	773
PTGS2	IL1A	P01583	767
PTGS2	TLR4	O00206	763
PTGS2	HMOX1	P09601	762

IntAct

Human interaction partners of PTGS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
ATN1	physical association	0.560	3
HLA-A	physical association	0.400	1
CASK	physical association	0.370	1
LMAN2L	association	0.350	1

BioGRID (99 interactions; top human partners by supporting records): TP53 (Affinity Capture-Western; 13 records), CAV1 (Affinity Capture-Western; 11 records), DERL1 (Affinity Capture-Western; 4 records), NUCB1 (Co-fractionation; 4 records), USP22 (Affinity Capture-Western; 4 records), COPS5 (Reconstituted Complex; 3 records), ELAVL1 (Protein-RNA; 3 records), AGTR1 (Affinity Capture-Western; 2 records), APP (Affinity Capture-Western; 2 records), COPS7A (Reconstituted Complex; 2 records), CTNNB1 (Protein-RNA; 2 records), DERL2 (Affinity Capture-Western; 2 records), ELMO1 (Affinity Capture-Western; 2 records), EP300 (Affinity Capture-Western; 2 records), LMAN2L (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 39 of 42 signaling interactions:

A	Effect	B	Mechanism
PTGS2	up-regulates	“prostaglandin D2”	“chemical modification”
PTGS2	up-regulates	“prostaglandin F2alpha”	“chemical modification”
PTGS2	up-regulates	Prostacycline	“chemical modification”
“acetylsalicylic acid”	down-regulates	PTGS2	“chemical inhibition”
PTGS2	down-regulates	GSK3B
celecoxib	down-regulates	PTGS2	“chemical inhibition”
Pravadoline	down-regulates	PTGS2	“chemical inhibition”
“arachidonic acid”	up-regulates	PTGS2
PTGS2	“up-regulates quantity”	“prostaglandin E2(1-)”	“chemical modification”
SRF	up-regulates	PTGS2
PTGS2	up-regulates	IL4
PTGS2	up-regulates	MYOD1
paracetamol	“down-regulates activity”	PTGS2	“chemical inhibition”
suprofen	“down-regulates activity”	PTGS2	“chemical inhibition”
ketoprofen	“down-regulates activity”	PTGS2	“chemical inhibition”
oxaprozin	“down-regulates activity”	PTGS2	“chemical inhibition”
NfKb-p65/p50	“up-regulates quantity by expression”	PTGS2
IRX1	“up-regulates quantity by expression”	PTGS2	“transcriptional regulation”
N	“up-regulates activity”	PTGS2	“transcriptional regulation”
S	“up-regulates activity”	PTGS2	“transcriptional regulation”
PTGS2	up-regulates	Inflammation
NFATC2	“up-regulates quantity by expression”	PTGS2	“transcriptional regulation”
NFATC1	“up-regulates quantity by expression”	PTGS2	“transcriptional regulation”
NFATC4	“up-regulates quantity by expression”	PTGS2	“transcriptional regulation”
NFATC3	“up-regulates quantity by expression”	PTGS2	“transcriptional regulation”
PTGS2	“down-regulates quantity”	“episterol ester”	“chemical modification”
PTGS2	“up-regulates quantity”	“prostaglandin E2”	binding
PTGS2	up-regulates	Metastasis
AML1-ETO	“up-regulates quantity by expression”	PTGS2	“transcriptional regulation”
indometacin	“down-regulates activity”	PTGS2	“chemical inhibition”
“5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid”	“down-regulates activity”	PTGS2	“chemical inhibition”
ibuprofen	“down-regulates activity”	PTGS2	“chemical inhibition”
naproxen	“down-regulates activity”	PTGS2	“chemical inhibition”
piroxicam	“down-regulates activity”	PTGS2	“chemical inhibition”
meloxicam	“down-regulates activity”	PTGS2	“chemical inhibition”
PTGS2	“up-regulates quantity”	“prostaglandin G2(1-)”	“chemical modification”
PTGS2	“up-regulates quantity”	“prostaglandin H2(1-)”	“chemical modification”
LYN	“up-regulates activity”	PTGS2	phosphorylation
FYN	“up-regulates activity”	PTGS2	phosphorylation

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
★ COX2 complex	1	PTGS2

Disease & clinical

Genetic variants

Variant evidence for PTGS2: 56 ClinVar records (0 pathogenic / likely pathogenic); 6 PharmGKB clinical annotations; 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	7
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 356):

Position(s)	Effect	Δscore	Sites
1:186674763–186674764	acceptor_loss	1.0000	4
1:186674773–186674774	acceptor_gain	1.0000	2
1:186675397	acceptor_loss	1.0000
1:186675399	acceptor_gain	1.0000
1:186675896–186675897	donor_loss	1.0000	5
1:186676831–186676832	donor_loss	1.0000	4
1:186676917	acceptor_loss	1.0000
1:186676924	acceptor_gain	1.0000
1:186676927	acceptor_gain	1.0000
1:186677647–186677648	donor_loss	1.0000	5

AlphaMissense

1,452 missense substitutions predicted likely pathogenic (of 3,995 scored), across 357 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
M259	9	0.862	0.944
M99	9	0.818	0.959
F367	8	0.983	0.999
F196	8	0.971	0.991
H295	8	0.967	0.990
F191	8	0.964	0.995
F504	8	0.956	0.983
H193	8	0.954	0.985
F536	8	0.954	0.991
H374	8	0.941	0.984
N296	8	0.926	0.994
F184	8	0.902	0.979
N361	8	0.899	0.988
D311	8	0.895	0.963
H190	8	0.891	0.989
F464	8	0.882	0.979
H372	8	0.879	0.987
N425	8	0.866	0.992
H212	8	0.858	0.948
F566	8	0.852	0.962

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Lung Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	0.000731

Disease associations

OMIM: gene MIM:600262 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST003044_110	Crohn’s disease	4e-9
GCST003043_152	Inflammatory bowel disease	2e-7
GCST000186_1	Knee osteoarthritis	3e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2094253 (PROTEIN FAMILY), CHEMBL230 (SINGLE PROTEIN), CHEMBL3885623 (PROTEIN FAMILY), CHEMBL4523964 (SELECTIVITY GROUP)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PTGS2 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.

16 curated-mechanism drugs:

Drug	Modality	Max phase
CARPROFEN	Small molecule	4
CELECOXIB	Small molecule	4
ETODOLAC	Small molecule	4
ETORICOXIB	Small molecule	4
LUMIRACOXIB	Small molecule	4
MELOXICAM	Small molecule	4
NABUMETONE	Small molecule	4
PARECOXIB	Small molecule	4
ROFECOXIB	Small molecule	4
VALDECOXIB	Small molecule	4
GW-406381	Small molecule	3
IGURATIMOD	Small molecule	3
POLMACOXIB	Small molecule	3
ACECLOFENAC	Small molecule	2
APRICOXIB	Small molecule	2
CIMICOXIB	Small molecule	2

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 PTGS2 — 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: 764,124 (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 192 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1316	CARPROFEN	4	32,910
CHEMBL118	CELECOXIB	4	113,751
CHEMBL622	ETODOLAC	4	58,336
CHEMBL416146	ETORICOXIB	4	32,540
CHEMBL404108	LUMIRACOXIB	4	21,345
CHEMBL599	MELOXICAM	4	50,465
CHEMBL1206690	PARECOXIB	4	22,194
CHEMBL122	ROFECOXIB	4	67,323
CHEMBL865	VALDECOXIB	4	41,977
CHEMBL291338	3,3’,4’,5-TETRACHLOROSALICYLANILIDE	4	727
CHEMBL3301610	ABEMACICLIB	4	7,497
CHEMBL3707348	ACALABRUTINIB	4	4,772
CHEMBL189171	ACEMETACIN	4	17,104
CHEMBL1085	ACETOPHENAZINE	4	5,157
CHEMBL600	ACETYLCYSTEINE	4	96,284
CHEMBL1224	ACRIVASTINE	4	11,190
CHEMBL682	AMODIAQUINE	4	7,237
CHEMBL267345	AMPHOTERICIN B	4	87,420
CHEMBL43	AMSACRINE	4	83,286
CHEMBL712	ANISINDIONE	4	2,609
CHEMBL53	APOMORPHINE	4
CHEMBL1363	ARFORMOTEROL	4
CHEMBL25	ASPIRIN	4
CHEMBL46740	BAZEDOXIFENE	4
CHEMBL1201250	BENZQUINAMIDE	4
CHEMBL1008	BEPRIDIL	4
CHEMBL1101	BIPERIDEN	4
CHEMBL1077	BROMFENAC	4
CHEMBL1200666	CALCIPOTRIENE	4
CHEMBL846	CALCITRIOL	4
CHEMBL1014	CANDESARTAN CILEXETIL	4
CHEMBL190461	CANNABIDIOL	4
CHEMBL294199	CAPSAICIN	4
CHEMBL1560	CAPTOPRIL	4
CHEMBL1435	CEFAZOLIN	4
CHEMBL528	CEFTIZOXIME	4
CHEMBL1604	CEPHRADINE	4
CHEMBL311498	CIANIDANOL	4
CHEMBL104	CLOTRIMAZOLE	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL178	DAUNORUBICIN	4
CHEMBL1200515	DESERPIDINE	4
CHEMBL175	DEXIBUPROFEN	4
CHEMBL75435	DEXKETOPROFEN	4
CHEMBL139	DICLOFENAC	4
CHEMBL1034	DICLOFENAC SODIUM	4
CHEMBL411	DIETHYLSTILBESTROL	4
CHEMBL926	DOBUTAMINE	4
CHEMBL53463	DOXORUBICIN	4
CHEMBL679	EPINEPHRINE	4
CHEMBL442	ERGOTAMINE	4
CHEMBL435298	ESFLURBIPROFEN	4
CHEMBL1255800	FIDAXOMICIN	4
CHEMBL255044	FLUPIRTINE	4
CHEMBL563	FLURBIPROFEN	4
CHEMBL2220442	FLUVASTATIN	4
CHEMBL1622	FOLIC ACID	4
CHEMBL146095	GLAFENINE	4
CHEMBL54	HALOPERIDOL	4
CHEMBL496	HEXACHLOROPHENE	4

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs12042763	Efficacy	3	aspirin	Prostatic Neoplasms
rs20417	Efficacy	3	aspirin	Coronary Artery Disease
rs20417	Efficacy	3	rofecoxib
rs20417	Efficacy	3	ibuprofen
rs4648287	Toxicity	3	atenolol	Hypertension
rs5275	Efficacy	3	capecitabine;oxaliplatin	Colorectal Neoplasms

PharmGKB variants

4 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5275	PTGS2	3	2.75	1	capecitabine;oxaliplatin
rs20417	PTGS2	3	2.50	3	rofecoxib;ibuprofen;aspirin
rs4648287	PTGS2	3	1.50	1	atenolol
rs12042763	PTGS2	3	2.50	1	aspirin

PharmGKB variant annotations

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

16 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs4648287	atenolol	Other	Allele G is associated with increased likelihood of Hypercholesterolemia due to atenolol in people with Hypertension as compared to allele A.	PMID:24116192
rs689466	celecoxib	Efficacy	Genotype CC is associated with increased response to celecoxib in healthy individuals as compared to genotypes CT + TT.	PMID:29066864
rs20417	rofecoxib	Efficacy	Genotype CC is associated with increased pain relief when treated with rofecoxib as compared to genotypes CG + GG.	PMID:16678543
rs20417	ibuprofen	Efficacy	Genotypes CG + GG are associated with increased pain relief when treated with ibuprofen as compared to genotype CC.	PMID:16678543
rs5275	capecitabine, oxaliplatin	Efficacy	Genotype AA is associated with increased progression-free survival and overall survival when treated with capecitabine and oxaliplatin in people with Colorectal Neoplasms as compared to genotypes AG + GG.	PMID:19219602
rs20417			Genotypes CG + GG are associated with decreased risk of Stroke as compared to genotype CC.	PMID:15138244
rs20417		Other	Genotypes CG + GG are associated with decreased risk of Myocardial Infarction as compared to genotype CC.	PMID:15138244
rs20417	omega-3 polyunsaturated fatty acids	Other	Genotypes CG + GG are associated with increased risk of Colonic Neoplasms when exposed to omega-3 polyunsaturated fatty acids as compared to genotype CC.	PMID:15150618
rs20417			Allele G is associated with increased risk of Stroke as compared to allele C.	PMID:17495879
rs20417	aspirin	Other	Allele G is associated with increased risk of Coronary Disease in people not taking aspirin as compared to allele C.	PMID:17495879
rs20417	aspirin	Other	Allele G is associated with decreased risk of Coronary Disease when treated with aspirin as compared to allele C.	PMID:17495879
rs5272	nimesulide	Metabolism/PK	Allele C is associated with increased enzyme activity of PTGS2 when treated with nimesulide.	PMID:20548327
rs5273	nimesulide	Metabolism/PK	Allele G is associated with increased enzyme activity of PTGS2 when treated with nimesulide.	PMID:20548327
rs4648276	Coxibs	Toxicity	Genotypes AG + GG are associated with increased likelihood of Acute coronary syndrome when exposed to Coxibs in people with Acute coronary syndrome as compared to genotype AA.	PMID:20538124
rs20417	Coxibs	Toxicity	Genotypes CG + GG are associated with increased likelihood of Acute coronary syndrome when exposed to Coxibs in people with Acute coronary syndrome as compared to genotype CC.	PMID:20538124
rs12042763	aspirin	Efficacy	Genotype GG is associated with decreased risk of Prostatic Neoplasms when exposed to aspirin as compared to genotypes GT + TT.	PMID:20688905

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Cyclooxygenase

Most potent curated ligand interactions (44 total), top 25:

Ligand	Action	Affinity	Parameter
NS-398	Inhibition	8.72	pIC50
GW406381	Inhibition	8.52	pIC50
benzquinamide	Inhibition	8.32	pIC50
SC-236	Inhibition	8.3	pIC50
valdecoxib	Inhibition	8.3	pIC50
flurbiprofen	Inhibition	8.0	pIC50
(S)-ARN2508	Inhibition	7.92	pIC50
diclofenac	Inhibition	7.7	pIC50
meclofenamic acid	Inhibition	7.4	pIC50
SC-58125	Inhibition	7.39	pIC50
peptide 30 [PMID: 27019010]	Inhibition	7.22	pIC50
tigemocoxib	Inhibition	7.2	pIC50
carprofen	Inhibition	6.99	pIC50
compound 3 [Uddin et al., 2020]	Inhibition	6.7	pIC50
compound 12a [PMID: 29031075]	Inhibition	6.64	pIC50
HR1405-01	Inhibition	6.52	pIC50
celecoxib	Inhibition	6.52	pIC50
rofecoxib	Inhibition	6.5	pIC50
lumiracoxib	Inhibition	6.49	pKi
compound 9 [Kumar et al., 2019]	Inhibition	6.44	pIC50
SWE101	Inhibition	6.38	pIC50
meloxicam	Inhibition	6.31	pIC50
nimesulide	Inhibition	6.22	pIC50
ketoprofen	Inhibition	6.16	pIC50
resveratrol	Inhibition	6.12	pIC50

Binding affinities (BindingDB)

2941 measured of 4170 human assays (5722 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(4-methoxyphenyl)-2-(4-(methylsulfonyl)phenyl)-1H-indole	IC50	0.02 nM
4-(5-methyl-3-phenyl-1H-indol-2-yl)benzenesulfonamide	IC50	0.02 nM
4-(3-p-tolyl-1H-indol-2-yl)benzenesulfonamide	IC50	0.07 nM
4-(3-phenyl-1H-indol-2-yl)benzenesulfonamide	IC50	0.09 nM
2-(4-(methylsulfonyl)phenyl)-3-p-tolyl-1H-indole	IC50	0.09 nM
4-(5-chloro-3-phenyl-1H-indol-2-yl)benzenesulfonamide	IC50	0.14 nM
3-(3,4-dimethylphenyl)-2-(4-(methylsulfonyl)phenyl)-1H-indole	IC50	0.17 nM
N-(4-(3-phenyl-1H-indol-2-yl)phenylsulfonyl)acetamide	IC50	0.18 nM
5-methyl-2-(4-(methylsulfonyl)phenyl)-3-phenyl-1H-indole	IC50	0.28 nM
{3-[4-(4-Bromo-phenyl)-thiazol-2-ylmethyl]-5-methoxy-2-methyl-indol-1-yl}-(4-chloro-phenyl)-methanone	IC50	0.3 nM
CHEMBL271173	IC50	0.3 nM
5-chloro-2-(4-(methylsulfonyl)phenyl)-3-phenyl-1H-indole	IC50	0.36 nM
3-(4-bromophenyl)-2-(4-(methylsulfonyl)phenyl)-1H-indole	IC50	0.37 nM
CHEMBL270293	IC50	0.4 nM
1-(12-chloro-10-tetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trienyl)-3-[1-(oxane-4-carbonyl)piperidin-4-yl]urea	IC50	0.4 nM	US-20240182406: COMPOUNDS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
1-(12-fluoro-10-tetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trienyl)-3-[1-(oxane-4-carbonyl)piperidin-4-yl]urea	IC50	0.4 nM	US-20240182406: COMPOUNDS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
1-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-(12-fluoro-10-tetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trienyl)urea	IC50	0.4 nM	US-20240182406: COMPOUNDS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid	IC50	0.5 nM
4-{3-[3-(3-Adamantan-1-yl-ureido)-propyl]-5-phenyl-pyrazol-1-yl}-benzenesulfonamide	IC50	0.5 nM
4-{3-[3-(3-Cycloheptyl-ureido)-propyl]-5-phenyl-pyrazol-1-yl}-benzenesulfonamide	IC50	0.5 nM
4-(5-Phenyl-3-{3-[3-(4-trifluoromethoxy-phenyl)-ureido]-propyl}-pyrazol-1-yl)-benzenesulfonamide	IC50	0.5 nM
4-(5-chloro-3-(4-chlorophenyl)-1H-indol-2-yl)benzenesulfonamide	IC50	0.54 nM
2-(4-(methylsulfonyl)phenyl)-3-phenyl-1H-indole	IC50	0.6 nM
CHEMBL1922660	IC50	0.7 nM
CHEMBL5267320	IC50	0.75 nM
CHEMBL5267685	IC50	0.77 nM
5-chloro-3-(3-chlorophenyl)-2-(4-(methylsulfonyl)phenyl)-1H-indole	IC50	0.8 nM
4-{5-Phenyl-3-[3-(3-phenyl-ureido)-propyl]-pyrazol-1-yl}-benzenesulfonamide	IC50	0.8 nM
4-(3-{3-[3-(4-Chloro-phenyl)-ureido]-propyl}-5-phenyl-pyrazol-1-yl)-benzenesulfonamide	IC50	0.8 nM
CHEMBL5274847	IC50	0.8 nM
CHEMBL5270325	IC50	0.8 nM
3,5-Bis-(4-fluoro-phenyl)-4-aza-tricyclo[5.2.1.0*2,6*]deca-2,5-diene	IC50	1 nM
[3-(4-Benzo[b]thiophen-3-yl-thiazol-2-ylmethyl)-5-methoxy-2-methyl-indol-1-yl]-(4-chloro-phenyl)-methanone	IC50	1 nM
CHEMBL3741490	IC50	1 nM
CHEMBL5206077	IC50	1 nM
CHEMBL1945285	IC50	1.2 nM
CHEMBL270078	IC50	1.2 nM
CHEMBL272433	IC50	1.2 nM
CHEMBL259972	IC50	1.4 nM
5-bromo-2-(4-(methylsulfonyl)phenyl)-3-phenyl-1H-indole	IC50	1.41 nM
4-(3-(3,4-dimethylphenyl)-1H-indol-2-yl)benzenesulfonamide	IC50	1.46 nM
CHEMBL5592921	IC50	1.8 nM
3-nitrooxypropyl 2-[1-(4-methoxyphenyl)-2-methyl-5-(4-methylsulfonylphenyl)pyrrol-3-yl]acetate	IC50	2 nM	US-9162979: 1,5-Diary1-2-alkylpyrrole-3-substituted nitro esters, selective COX-2 inhibitors and nitric oxide donors
4-(5-Fluoromethyl-3-phenyl-isoxazol-4-yl)-benzenesulfonamide	IC50	2 nM
L-689037	IC50	2 nM
4-(5-fluoro-3-phenyl-1H-indol-2-yl)benzenesulfonamide	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
CHEMBL316846	IC50	2 nM
CHEMBL5267453	IC50	2 nM

ChEMBL bioactivities

5553 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL499069
10.70	IC50	0.02	nM	CHEMBL501208
10.70	IC50	0.02	nM	CHEMBL525247
10.16	IC50	0.06998	nM	CHEMBL502555
10.15	IC50	0.07	nM	CHEMBL502555
10.10	IC50	0.08	nM	CHEMBL143776
10.05	IC50	0.09	nM	CHEMBL524543
10.05	IC50	0.09	nM	CHEMBL500936
10.05	IC50	0.08995	nM	CHEMBL524543
10.05	IC50	0.08995	nM	CHEMBL500936
10.05	IC50	0.09	nM	THIOSEMICARBAZIDE
9.92	IC50	0.12	nM	CHEMBL140167
9.85	IC50	0.14	nM	CHEMBL499349
9.85	IC50	0.14	nM	INDOMETHACIN
9.77	IC50	0.17	nM	CHEMBL525021
9.77	IC50	0.1698	nM	CHEMBL525021
9.74	IC50	0.18	nM	CHEMBL500943
9.74	IC50	0.1799	nM	CHEMBL500943
9.73	IC50	0.188	nM	CHEMBL4582020
9.72	Kd	0.19	nM	CHEMBL1957450
9.70	IC50	0.2	nM	CHEMBL1958349
9.60	IC50	0.25	nM	CHEMBL551829
9.55	IC50	0.28	nM	CHEMBL525250
9.55	IC50	0.2799	nM	CHEMBL525250
9.55	IC50	0.28	nM	CHEMBL551148
9.52	IC50	0.3	nM	CHEMBL271173
9.52	IC50	0.3	nM	CHEMBL423296
9.44	IC50	0.36	nM	CHEMBL502285
9.44	IC50	0.3597	nM	CHEMBL502285
9.43	IC50	0.37	nM	CHEMBL502554
9.43	IC50	0.3698	nM	CHEMBL502554
9.40	IC50	0.4	nM	CHEMBL270293
9.36	IC50	0.44	nM	CHEMBL186632
9.35	IC50	0.45	nM	CHEMBL282093
9.33	Ki	0.47	nM	CELECOXIB
9.30	IC50	0.5	nM	CHEMBL561891
9.30	IC50	0.5	nM	CHEMBL108201
9.28	IC50	0.52	nM	CELECOXIB
9.27	IC50	0.54	nM	CHEMBL500674
9.27	IC50	0.5395	nM	CHEMBL500674
9.22	IC50	0.6	nM	CHEMBL499070
9.22	IC50	0.5998	nM	CHEMBL499070
9.10	IC50	0.8	nM	CHEMBL500675
9.10	IC50	0.7998	nM	CHEMBL500675
9.00	IC50	1	nM	CHEMBL327384
9.00	IC50	1	nM	CHEMBL88717
9.00	IC50	1	nM	CHEMBL432945
9.00	IC50	1	nM	CHEMBL313387
9.00	IC50	1	nM	CHEMBL5089355
9.00	IC50	1	nM	CHEMBL5200454

PubChem BioAssay actives

2593 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
4-[3-(4-methoxyphenyl)-1H-indol-2-yl]benzenesulfonamide	362870: Inhibition of COX2	ic50	<0.0001	uM
3-(4-methoxyphenyl)-2-(4-methylsulfonylphenyl)-1H-indole	362870: Inhibition of COX2	ic50	<0.0001	uM
3-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-1H-indole	362870: Inhibition of COX2	ic50	<0.0001	uM
4-[3-(4-(111C)methoxyphenyl)-1H-indol-2-yl]benzenesulfonamide	1896014: Inhibition of COX2 (unknown origin)	ic50	<0.0001	uM
3-(4-methylphenyl)-2-(4-methylsulfonylphenyl)-1H-indole	362870: Inhibition of COX2	ic50	0.0001	uM
4-(3-phenyl-1H-indol-2-yl)benzenesulfonamide	362870: Inhibition of COX2	ic50	0.0001	uM
4-[3-(4-methylphenyl)-1H-indol-2-yl]benzenesulfonamide	362870: Inhibition of COX2	ic50	0.0001	uM
4-(5-chloro-3-phenyl-1H-indol-2-yl)benzenesulfonamide	362870: Inhibition of COX2	ic50	0.0001	uM
3-(3,4-dimethylphenyl)-2-(4-methylsulfonylphenyl)-1H-indole	362870: Inhibition of COX2	ic50	0.0002	uM
N-[(4-fluorophenyl)methyl]-4-(4-methylsulfonylphenyl)-6-(trifluoromethyl)pyrimidin-2-amine	432545: Inhibition of human COX2 expressed in african green monkey COS cells assessed as inhibition of arachidonic acid-stimulated PGE2 production treated 1 hr before arachidonic acid challenge by enzyme immunoassay	ic50	0.0003	uM
4-[2-(4-ethoxyphenyl)pyrazolo[1,5-b]pyridazin-3-yl]benzenesulfonamide	241308: Inhibition of human cyclooxygenase-2 expressed in COS cells	ic50	0.0004	uM
5-chloro-2-(4-methylsulfonylphenyl)-3-phenyl-1H-indole	362870: Inhibition of COX2	ic50	0.0004	uM
1-methoxy-4-[2-(4-methylsulfonylphenyl)cyclopenten-1-yl]benzene	162346: In vitro inhibition of prostaglandin G/H synthase 2 (COX-2).	ic50	0.0005	uM
2-(4-methylsulfonylphenyl)-3-phenyl-1H-indole	362870: Inhibition of COX2	ic50	0.0006	uM
4-[6-(3,4-dichlorophenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0010	uM
[3-[[4-(1-benzothiophen-3-yl)-1,3-thiazol-2-yl]methyl]-5-methoxy-2-methylindol-1-yl]-(4-chlorophenyl)methanone	162658: Inhibitory concentration against human recombinant Prostaglandin G/H synthase 2 cloned and expressed in baculovirus (Sf9)	ic50	0.0010	uM
4-[5-[4-(trifluoromethyl)phenyl]spiro[2.4]hept-5-en-6-yl]benzenesulfonamide	162653: Inhibitory activity against prostaglandin G/H synthase 2 (COX-2).	ic50	0.0010	uM
6-(4-chlorophenyl)-5-(4-methylsulfonylphenyl)spiro[2.4]hept-5-ene	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0010	uM
4-[6-(4-chlorophenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0010	uM
4-[5-(4-methoxyphenyl)spiro[2.4]hept-5-en-6-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0010	uM
5-[[1-[(2S)-2-hydroxy-3-(5-hydroxy-4-oxo-2-phenylchromen-7-yl)oxypropyl]indol-3-yl]methylidene]-1,3-diazinane-2,4,6-trione	1810792: Inhibition of human COX-2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA	ic50	0.0010	uM
4-(111C)methoxy-6-(4-methylsulfonylphenyl)-N-(thiophen-2-ylmethyl)pyrimidin-2-amine	1896014: Inhibition of COX2 (unknown origin)	ic50	0.0010	uM
phenyl 5-methyl-3-(4-methylphenyl)pyrazole-1-sulfonate	1752430: Inhibition of human recombinant COX-2 assessed as production of PGE2 using arachidonic acid as a substrate preincubated for 60 mins followed by substrate addition and measured after 2 mins by ELISA analysis	ic50	0.0011	uM
[4-[3-(4-methylsulfonylphenyl)-5-oxo-2H-furan-4-yl]phenyl] acetate	162503: In vitro inhibitory concentration of compound required to inhibit Prostaglandin G/H synthase 2 enzyme was determined	ic50	0.0013	uM
6-(3-bromo-4-methoxyphenyl)-5-(4-methylsulfonylphenyl)spiro[2.4]hept-5-ene	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0013	uM
(3E)-1-(2,6-dichlorophenyl)-3-[(4-oxochromen-3-yl)methylidene]indol-2-one	1177989: Inhibition of human recombinant COX-2 assessed as decrease in prostaglandin production using arachidonic acid as substrate incubated with enzyme for 10 mins prior to substrate challenge by enzyme immunoassay	ic50	0.0013	uM
4-[3-(3,4-dimethylphenyl)-1H-indol-2-yl]benzenesulfonamide	362870: Inhibition of COX2	ic50	0.0015	uM
4-[6-(3-chloro-4-fluorophenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0015	uM
5-(4-methylphenyl)-6-(4-methylsulfonylphenyl)spiro[2.4]hept-5-ene	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0015	uM
[3-[3-(4-methylsulfonylphenyl)-5-oxo-2H-furan-4-yl]phenyl] acetate	162503: In vitro inhibitory concentration of compound required to inhibit Prostaglandin G/H synthase 2 enzyme was determined	ic50	0.0017	uM
4-[4-fluoro-5-phenyl-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide	162507: In vitro inhibitory concentration required to block human recombinant prostaglandin G/H synthase 2 (COX-2)	ic50	0.0017	uM
4-[4-(18F)fluoro-5-phenyl-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide	1896014: Inhibition of COX2 (unknown origin)	ic50	0.0017	uM
4-phenyl-3-[4-(2H-tetrazol-5-yl)phenyl]-2H-furan-5-one	270014: Inhibition of COX2	ic50	0.0018	uM
5-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-2H-tetrazole	270014: Inhibition of COX2	ic50	0.0019	uM
4-[2-(3-chloro-4-fluorophenyl)-4,5-difluorophenyl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
4-[2-(3,4-dichlorophenyl)cyclopenten-1-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
4-[4,5-difluoro-2-(4-fluoro-3-methylphenyl)phenyl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
4-[6-(3-bromo-4-methoxyphenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
4-[2-(4-methoxyphenyl)cyclopenten-1-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
6-(4-methylsulfonylphenyl)-5-[4-(trifluoromethyl)phenyl]spiro[2.4]hept-5-ene	162653: Inhibitory activity against prostaglandin G/H synthase 2 (COX-2).	ic50	0.0020	uM
4-[6-(3-fluoro-4-methoxyphenyl)spiro[2.4]hept-5-en-5-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
4-[2-(1,3-benzodioxol-5-yl)cyclopenten-1-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
4-[2-[3-chloro-4-(dimethylamino)phenyl]cyclopenten-1-yl]benzenesulfonamide	160434: Inhibition of human Prostaglandin G/H synthase 2	ic50	0.0020	uM
1-(3-chloro-4-fluorophenyl)-4,5-difluoro-2-(4-methylsulfonylphenyl)benzene	1532167: Inhibition of recombinant human COX-2 expressed in Baculovirus infected sf9 cells using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by ELISA	ic50	0.0020	uM
3-(4-methylsulfonylphenyl)-2-phenylpyrazolo[1,5-b]pyridazine	241308: Inhibition of human cyclooxygenase-2 expressed in COS cells	ic50	0.0020	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
4-(5-fluoro-3-phenyl-1H-indol-2-yl)benzenesulfonamide	362870: Inhibition of COX2	ic50	0.0020	uM
(7E)-5-methyl-3-(5-nitrothiophen-2-yl)-7-[(5-nitrothiophen-2-yl)methylidene]-2-phenyl-3,3a,4,6-tetrahydropyrazolo[4,3-c]pyridine	1939574: Inhibition of COX-2 (unknown origin) using arachidonic acid as substrate incubated for 1 min by absorbance based analysis	ic50	0.0020	uM
2-[4-[4-(trifluoromethyl)phenyl]triazol-1-yl]ethyl 4-methylsulfonylbenzoate	1939590: Inhibition of human COX-2 using arachidonic acid as substrate incubated for 30 secs by ELISA	ic50	0.0020	uM
(7E)-3-(5-bromothiophen-2-yl)-7-[(5-bromothiophen-2-yl)methylidene]-5-methyl-2-phenyl-3,3a,4,6-tetrahydropyrazolo[4,3-c]pyridine	1939574: Inhibition of COX-2 (unknown origin) using arachidonic acid as substrate incubated for 1 min by absorbance based analysis	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dinoprostone	decreases response to substance, affects abundance, affects chemical synthesis, decreases reaction, increases activity (+11 more)	58
Lipopolysaccharides	increases expression, increases reaction, decreases reaction, increases abundance, increases secretion (+6 more)	57
Resveratrol	decreases reaction, increases expression, affects reaction, affects cotreatment, increases activity (+7 more)	51
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression, increases chemical synthesis, affects reaction, increases reaction (+4 more)	34
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	decreases activity, decreases expression, increases response to substance, decreases response to substance, decreases reaction (+11 more)	33
Celecoxib	affects reaction, decreases activity, decreases reaction, increases expression, increases reaction (+7 more)	32
Particulate Matter	increases reaction, affects expression, decreases reaction, increases abundance, increases secretion (+4 more)	32
Acetylcysteine	increases abundance, decreases reaction, increases expression, affects cotreatment, decreases expression (+2 more)	28
Quercetin	decreases secretion, increases reaction, decreases reaction, affects binding, increases activity (+5 more)	27
SB 203580	increases expression, decreases degradation, increases chemical synthesis, increases abundance, decreases reaction (+4 more)	26
Curcumin	increases reaction, decreases expression, increases expression, decreases reaction, affects cotreatment (+2 more)	22
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases secretion, increases chemical synthesis, affects localization (+2 more)	20
Tetrachlorodibenzodioxin	affects expression, decreases expression, decreases reaction, increases expression, affects binding (+3 more)	20
sodium arsenite	increases expression, affects reaction, increases reaction, affects response to substance, decreases expression (+1 more)	19
Indomethacin	affects cotreatment, decreases expression, decreases reaction, increases activity, decreases activity (+3 more)	19
bisphenol A	increases methylation, affects binding, affects response to substance, affects reaction, decreases reaction (+4 more)	17
Dexamethasone	affects cotreatment, decreases expression, decreases reaction, increases expression, increases activity (+2 more)	17
U 0126	affects reaction, affects cotreatment, decreases activity, decreases reaction, increases expression (+2 more)	16
Aspirin	decreases activity, decreases expression, increases reaction, decreases degradation, affects response to substance (+4 more)	16
nimesulide	affects abundance, affects chemical synthesis, increases metabolic processing, decreases activity, affects expression (+6 more)	15
Vehicle Emissions	increases abundance, increases expression, affects cotreatment, affects binding, decreases reaction (+4 more)	15
Estradiol	affects cotreatment, decreases reaction, increases expression, increases reaction, affects expression (+2 more)	13
pyrazolanthrone	decreases reaction, increases expression, increases chemical synthesis, increases reaction	12
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, affects cotreatment, increases reaction, decreases expression	11
Arsenic Trioxide	increases expression, increases reaction, affects reaction, decreases expression, decreases reaction (+2 more)	11
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases reaction, increases expression, increases abundance	10
Cisplatin	increases expression, affects expression, affects reaction, affects cotreatment, decreases expression (+3 more)	10
Flurbiprofen	increases chemical synthesis, increases reaction, decreases activity, increases activity, decreases reaction (+1 more)	10
Tobacco Smoke Pollution	increases expression, increases abundance, decreases reaction	10
Arachidonic Acid	affects binding, decreases reaction, increases expression, increases activity, increases response to substance (+6 more)	10

ChEMBL screening assays

1548 unique, capped per target: 1478 binding, 35 functional, 34 admet, 1 toxicity

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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1H3	Abcam A-549 PTGS2 KO	Cancer cell line	Male
CVCL_B2CQ	Abcam HeLa PTGS2 KO	Cancer cell line	Female
CVCL_D7YV	Ubigene A-549 PTGS2 KO	Cancer cell line	Male
CVCL_E0M6	Ubigene HeLa PTGS2 KO	Cancer cell line	Female
CVCL_KT48	HeLa SilenciX COX2	Cancer cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00168987	Phase 4	COMPLETED	Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors
NCT00280709	Phase 4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00797121	Phase 4	UNKNOWN	Preoperative Biliary Drainage for Resectable Hilar Cholangiocarcinoma
NCT01111591	Phase 4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	Phase 4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01256047	Phase 4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy
NCT01642875	Phase 4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT02027311	Phase 4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02174575	Phase 4	WITHDRAWN	Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery
NCT07486713	Phase 4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT00540735	Phase 3	TERMINATED	Efficiency Evaluation of Photodynamic Therapy With Photofrin® on Unresectable Type III or IV Cholangiocarcinomas
NCT00653978	Phase 3	UNKNOWN	Unilateral Versus Bilateral Stents for Bismuth Type II and III Malignant Hilar Strictures
NCT00809081	Phase 3	UNKNOWN	Early Enteral Feeding After Pylorus Preserving Pancreatoduodenectomy
NCT00869635	Phase 3	COMPLETED	S-1 and Photodynamic Therapy in Cholangiocarcinoma
NCT00907413	Phase 3	TERMINATED	Photodynamic Therapy (PDT) Trial for Palliation of Cholangiocarcinoma
NCT01926236	Phase 3	COMPLETED	Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
NCT02170090	Phase 3	ACTIVE_NOT_RECRUITING	Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
NCT02548195	Phase 3	UNKNOWN	Oxaliplatin+Gemcitabine vs Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma
NCT02773485	Phase 3	UNKNOWN	Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma
NCT02853474	Phase 3	COMPLETED	Early Palliative Care in Patients With Metastatic Upper Gastrointestinal Cancers Treated With First-line Chemotherapy
NCT02989857	Phase 3	COMPLETED	Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
NCT03656536	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma
NCT03773302	Phase 3	TERMINATED	Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
NCT03779035	Phase 3	UNKNOWN	Adjuvant Chemotherapy for Biliary Tract Cancer After Curative Resection
NCT04093362	Phase 3	TERMINATED	Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements
NCT04157985	Phase 3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT05823311	Phase 3	RECRUITING	Lenvatinib, Tislelizumab Combined with Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma
NCT05876754	Phase 3	ACTIVE_NOT_RECRUITING	An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
NCT05948475	Phase 3	ACTIVE_NOT_RECRUITING	Study of Tinengotinib VS. Physician’s Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma
NCT07155525	Phase 3	RECRUITING	Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas
NCT07328919	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
NCT00286013	Phase 2	COMPLETED	Feasibility of Radiotherapy and Concomitant Gemcitabine and Oxaliplatin in Locally Advanced Pancreatic Cancer and Distal Cholangiocarcinoma
NCT00290316	Phase 2	UNKNOWN	Accuracy of Endoscopic Ultrasound for Detection of Tumors of the Liver
NCT00350753	Phase 2	COMPLETED	Avastin and Tarceva for Upper Gastrointestinal Cancers
NCT00356161	Phase 2	UNKNOWN	HAI Via Interventionally Implanted Port Catheter Systems
NCT00660140	Phase 2	COMPLETED	Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer
NCT00713687	Phase 2	WITHDRAWN	Gemcitabine/Oxaliplatin and Photodynamic Therapy in Cholangiocarcinoma
NCT00779454	Phase 2	COMPLETED	Combined Biological Treatment and Chemotherapy for Patients With Inoperable Cholangiocarcinoma
NCT00832637	Phase 2	TERMINATED	Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers
NCT00948935	Phase 2	COMPLETED	Study of Gemcitabine, Irinotecan and Panitumumab in Patients With Advanced and Metastatic Biliary Tract Adenocarcinoma
NCT00973713	Phase 2	UNKNOWN	Study of RAD001 in Advanced Cholangiocarcinoma: RADiChol
NCT00975039	Phase 2	TERMINATED	Study Using WST11 in Patients With Non-Resectable or Inoperable Cholangiocarcinoma
NCT01007552	Phase 2	COMPLETED	A Study of Gemcitabine, Capecitabine and Bevacizumab to Treat Cancer of the Gall Bladder or Bile Ducts
NCT01043172	Phase 2	COMPLETED	A Study of Gemcitabine as an Adjuvant Treatment for Cholangiocarcinoma After Surgical Resection
NCT01151761	Phase 2	TERMINATED	Phase II SBRT & Chemo for Unresectable Cholangiocarcinoma Followed by Liver Transplantation
NCT01206049	Phase 2	COMPLETED	Combination Chemotherapy Plus Panitumumab or Bevacizumab for Inoperable Cholangiocarcinoma Without KRAS Mutations
NCT01247337	Phase 2	COMPLETED	Intra-hepatic Chemotherapy in Patient With Non-resectable Liver Metastases From Cholangiocarcinoma
NCT01267344	Phase 2	COMPLETED	A Randomized Study of GEMOX With or Without Cetuximab in Locally Advanced and Metastatic BTC
NCT01290536	Phase 2	COMPLETED	Yttrium-90 Radioembolization Using Glass Microspheres (TheraSphere) for Patients With Liver Metastases
NCT01317069	Phase 2	UNKNOWN	A Randomized, Open, Prospective Clinical Research of Fluorouracil Implant to Improve Surgical Gallbladder Cancer and Bile Duct Cancer
NCT01320241	Phase 2	COMPLETED	Radiation Stent Versus Self-expanding Metallic Stents (SEMS) for Palliative Treatment of Malignant Biliary Stricture
NCT01320254	Phase 2	COMPLETED	PiCCA Study (Panitumumab in Combination With Cisplatin/Gemcitabine)
NCT01501604	Phase 2	WITHDRAWN	BKM120 in Cancers With PIK3CA Activating Mutations
NCT01525719	Phase 2	UNKNOWN	Single Arm Study of RAD001 as Monotherapy in Treatment in Advanced Cholangiocarcinoma
NCT01855724	Phase 2	TERMINATED	Clinical Trial to Investigate the Efficacy of Treatment With Gemcitabine/Pazopanib in Patients With Biliary Tree Cancer
NCT01862315	Phase 2	COMPLETED	Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)
NCT01912053	Phase 2	COMPLETED	Efficacy Study of Intra-hepatic Administration of Therasphere® in Association With Intravenous Chemotherapy to Treat Cholangiocarcinoma
NCT01954745	Phase 2	COMPLETED	Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma
NCT01963325	Phase 2	COMPLETED	S-1 in Combination With Abraxane in Treating Cholangiocarcinoma
NCT02150967	Phase 2	TERMINATED	A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PTGS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.