PTGER3

Summary

PTGER3 (prostaglandin E receptor 3, HGNC:9595) is a protein-coding gene on chromosome 1p31.1, encoding Prostaglandin E2 receptor EP3 subtype (P43115). Receptor for prostaglandin E2 (PGE2).

The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor may have many biological functions, which involve digestion, nervous system, kidney reabsorption, and uterine contraction activities. Studies of the mouse counterpart suggest that this receptor may also mediate adrenocorticotropic hormone response as well as fever generation in response to exogenous and endogenous stimuli. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5733 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 65 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_198719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9595
Approved symbol	PTGER3
Name	prostaglandin E receptor 3
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	EP3, lnc003875
Ensembl gene	ENSG00000050628
Ensembl biotype	protein_coding
OMIM	176806
Entrez	5733

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 nonsense_mediated_decay

ENST00000306666, ENST00000356595, ENST00000361210, ENST00000370924, ENST00000370931, ENST00000460330, ENST00000479353, ENST00000497146, ENST00000628037, ENST00000865232

RefSeq mRNA: 7 — MANE Select: NM_198719 NM_001126044, NM_198714, NM_198715, NM_198716, NM_198717, NM_198718, NM_198719

CCDS: CCDS44160, CCDS652, CCDS655, CCDS656, CCDS657, CCDS658

Canonical transcript exons

ENST00000306666 — 4 exons

Exon	Start	End
ENSE00001313782	70970782	70971733
ENSE00001367103	70974297	70974388
ENSE00001426446	71012305	71012484
ENSE00003924332	71046681	71047816

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 95.41.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1876 / max 387.1816, expressed in 578 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12814	5.8367	553
201547	0.1347	75
201548	0.1114	64
12813	0.1049	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	95.41	gold quality
adult mammalian kidney	UBERON:0000082	95.16	gold quality
body of uterus	UBERON:0009853	94.77	gold quality
renal medulla	UBERON:0000362	94.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.49	gold quality
kidney	UBERON:0002113	92.82	gold quality
cauda epididymis	UBERON:0004360	92.53	gold quality
myometrium	UBERON:0001296	91.86	gold quality
vena cava	UBERON:0004087	91.69	gold quality
choroid plexus epithelium	UBERON:0003911	91.61	gold quality
kidney epithelium	UBERON:0004819	91.40	gold quality
adipose tissue	UBERON:0001013	91.28	gold quality
upper arm skin	UBERON:0004263	91.24	gold quality
metanephros cortex	UBERON:0010533	90.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.24	gold quality
connective tissue	UBERON:0002384	90.12	gold quality
omental fat pad	UBERON:0010414	89.93	gold quality
peritoneum	UBERON:0002358	89.92	gold quality
cortex of kidney	UBERON:0001225	89.59	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.46	gold quality
upper leg skin	UBERON:0004262	88.50	gold quality
smooth muscle tissue	UBERON:0001135	88.46	gold quality
lower lobe of lung	UBERON:0008949	88.22	silver quality
popliteal artery	UBERON:0002250	88.07	gold quality
parietal pleura	UBERON:0002400	88.06	gold quality
tibial artery	UBERON:0007610	88.04	gold quality
gingival epithelium	UBERON:0001949	87.94	gold quality
descending thoracic aorta	UBERON:0002345	87.93	gold quality
aorta	UBERON:0000947	87.83	gold quality
body of tongue	UBERON:0011876	87.76	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	262.25
E-CURD-119	yes	46.11
E-HCAD-10	yes	15.19
E-ANND-3	yes	6.78
E-MTAB-11268	no	326.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HOXA10

Literature-anchored findings (GeneRIF, showing 40)

• Functional analysis of the mouse counterpart. (PMID:12642666)
• expression of prostaglandin E receptor 3-2 was significantly lower in gravid than nongravid myometrium while levels of the prostaglandin E receptor 3-6 message were higher in gravid samples than in nongravid specimens (PMID:12699873)
• biochemical pathway exists wherein fluid shear activates cyclooxygenase-2, via a c-Jun N-terminal kinase2/c-Jun-dependent pathway, which in turn elicits downstream prostaglandin EP2 and EP3a1 receptor mRNA synthesis (PMID:12743126)
• An agonist of EP(3), an inhibitory pathway, antagonized activity levels induced by PGE(2). Generally reflective of changes in aromatase protein expression and the pattern of mRNA expression. (PMID:12788892)
• Human corpus cavernosum and cultured smooth muscle cells express EP1, EP2 and EP3 receptors. (PMID:14562138)
• role of araomatic amino acids in i2 loop in Gs coupling (PMID:14699136)
• EP3 and EP4 mediate different actions of PGE2 on mature human osteoclasts. Activation of EP4 receptors inhibits actin ring formation and activation of EP3 receptors increases number of lamellipodia. (PMID:15290741)
• When expressed in HEK293 cells, the isoforms located to the cell surface, although a fraction of some remained in the cell. (PMID:15304361)
• Prostaglandin (PG)E2 augments intracellular calcium levels in the T-leukemic cell line Jurkat through the E-prostanoid (EP)3 receptor. (PMID:15528329)
• EP3 receptors produce epidermal growth inhibition through the action of Ddiacylglycerol and ceramide second messengers. (PMID:16274459)
• analysis of a prostaglandin EP3alpha receptor intracellular loop peptide by NMR (PMID:16707103)
• the association between EH and nucleotide polymorphisms in the gene encoding the prostaglandin E2 receptor subtype EP2 (PTGER2). (PMID:17644362)
• Study indicates that genetic variations (single nucleotide polymorphism 1388T>C) in the Ptger3 gene are significantly associated with the risk and severity of asthma in the Korean population. (PMID:17877755)
• Expression of prostaglandin E(2) receptors (EP(2), EP(3), EP(4)), prostaglandin D(2) receptor (DP(2)), prostanoid thromboxane A(2) receptor (TP) and to a lesser extent EP(1) were observed in several hair follicle compartments. (PMID:18005048)
• We identified a new mRNA splice variant of the EP3 gene in human gastric fundic mucosa, mammary artery and pulmonary vessels. This EP3-Ic transcript contains exons 1, 2, 3, 5 and 6 of the EP3 gene and should be translated in the EP3-I isoform. (PMID:18023986)
• results showed that EP3 is expressed in trigeminal neurons (53% of total neurons), and is co-expressed in TRPV(1)-positive neurons (67 % of TRPV(1)-positive neurons. (PMID:18296611)
• Data suggest that expression of prostanoid receptors (prostaglandin E2 EP3-I, prostacyclin, and thromboxane A2 receptors) in vascular inflammation could influence cell responses dependent on the constitutive activation of ghrelin receptors. (PMID:18573679)
• EP3 receptors are involved in bladder micturition at supraspinal and spinal centers and in bladder nociception at the spinal cord (PMID:18632791)
• This study found that the non-conserved S211 and R214 of the hEP3 are involved in PGE(2) recognition. (PMID:18652829)
• Stimulation of the EP3(I) isoform of the human EP3 receptor with prostaglandin E(2) increases the mRNA expression of both VEGF and its cognate receptor VEGF receptor-1. (PMID:18996083)
• examined the contributions of EP3 to platelet function using the selective EP3 agonist sulprostone and also PGE(2) (PMID:19012178)
• In human parturition, there is decreased mRNA expression of lower-uterine segment EP3 receptor isoforms II and VI during labour. (PMID:19165680)
• EP3 receptor signaling on endothelial cells is essential for the MMP-9 upregulation that enhances tumor metastasis and angiogenesis. (PMID:19799610)
• The present results address the novel activities of COX-2/PGE2-EP3/EP4 signaling that modulate tumor biology and show that CXCL12/CXCR4 axis may play a crucial role in tumor stromal formation and angiogenesis under the control of prostaglandins. (PMID:20110411)
• Studies indicate assocation of PTGER3 and PON1 genotypes with preterm birth. (PMID:20140262)
• downregulated in endometriosis tissues (PMID:20452033)
• EP3 regulates VM and the associated increased MMP-2 enzyme activity. (PMID:20503412)
• E prostanoid (EP) 2 and EP3 have roles in cAMP/protein kinase A- and PI3-K/Akt-dependent NF-kappaB activation during shear-induced interleukin-6 synthesis in chondrocytes (PMID:20516073)
• lower levels in the conjunctival epithelial cells of Stevens-Johnson syndrome patients (PMID:20947153)
• The role of PGE(2) in human atherosclerotic plaque on platelet EP(3) and EP(4) receptor activation and platelet function in whole blood. (PMID:21424266)
• Data indicate that not only Cox-2 but also EP1 and EP3 could be important targets for chemosensitization and inhibition of metastasis in breast cancers that are resistant to chemotherapy. (PMID:21813027)
• A positive feedback pathway involving COX-2/PGE2/EP3 receptor-dependent EGFR reactivation exaggerates IL-8 production in NCI-H292 cancer cells but not in NHBE (normal) cells. (PMID:21925169)
• Data posit an association between the down-regulation of EP3 in conjunctival epithelium and the pathogenesis and pathology of SJS/TEN and OCP, and suggest a common mechanism(s) in the pathology of these diseases. (PMID:21966456)
• A novel dendritic cell(DC) progenitor regulatory pathway in which PGE(2) signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal progenitor survival and differentiation. (PMID:22110249)
• EP3 is the primary receptor subtype that mediates PGE(2) induced contractility in human pregnant myometrium at term and represents a possible therapeutic target. (PMID:22162473)
• Neuroblastoma express all four forms of PGE(2) receptors. (PMID:22276108)
• Prostaglandin E2 induced contraction of human intercostal arteries is mediated by the EP3 receptor (PMID:22342278)
• The levels of prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin-endoperoxide receptor 3 (PTGER3) mRNA are increased in patient with schizophrenia. (PMID:22397921)
• epistatic interaction with prostaglandin E receptor 3 gene confers an increased risk for Stevens-Johnson syndrome with severe ocular surface complications (PMID:22421267)
• laropiprant by itself attenuated platelet activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor stimulation, as demonstrated in assays of platelet aggregation (PMID:22870195)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptger3	ENSDARG00000055781
mus_musculus	Ptger3	ENSMUSG00000040016
rattus_norvegicus	Ptger3	ENSRNOG00000010325
drosophila_melanogaster	CG7497	FBGN0036742

Paralogs (7): TBXA2R (ENSG00000006638), PTGFR (ENSG00000122420), PTGER2 (ENSG00000125384), PTGIR (ENSG00000160013), PTGER1 (ENSG00000160951), PTGDR (ENSG00000168229), PTGER4 (ENSG00000171522)

Protein

Protein identifiers

Prostaglandin E2 receptor EP3 subtype — P43115 (reviewed: P43115)

Alternative names: PGE2-R, Prostanoid EP3 receptor

All UniProt accessions (3): A0A0B4J204, P43115, O00325

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for prostaglandin E2 (PGE2). The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G(i) proteins, and to an elevation of intracellular calcium. Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality.

Subunit / interactions. Interacts (via C-terminus) with MKLN1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in kidney. Expressed in small intestine, heart, pancreas, gastric fundic mucosa, mammary artery and pulmonary vessels.

Miscellaneous. Known as EP3D in PubMed:8075855. Known as EP3E in PubMed:8075855. Known as EP3F in PubMed:8075855.

Similarity. Belongs to the G-protein coupled receptor 1 family.

Isoforms (12)

UniProt ID	Names	Canonical?
P43115-1	EP3A, EP3-I, EP3a1, EP3a2, EP(3-Ic)	yes
P43115-2	EP3C, EP3-II
P43115-3	EP3B, EP3-III
P43115-4	EP3D, EP3-IV
P43115-5	EP3E
P43115-6	EP3F
P43115-7	EP3G
P43115-8	EP3-III
P43115-9	EP3-IV
P43115-10	EP3-V
P43115-11	EP3E2
P43115-12	12

RefSeq proteins (7): NP_001119516, NP_942007, NP_942008, NP_942009, NP_942010, NP_942011, NP_942012* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000265	Prostglndn_EP3_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR001244	Prostglndn_DP_rcpt	Family
IPR001481	EP3_rcpt_2	Family
IPR008365	Prostanoid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (50 total): splice variant 11, helix 11, topological domain 8, transmembrane region 7, sequence variant 4, strand 3, glycosylation site 2, turn 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6M9T	X-RAY DIFFRACTION	2.5
6AK3	X-RAY DIFFRACTION	2.9
7WU9	ELECTRON MICROSCOPY	3.38
8GDC	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43115-F1	76.06	0.41

Antibody-complex structures (SAbDab): 1 — 7WU9

Functional residue map

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

Glycosylation sites (2): 18, 36

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-391908	Prostanoid ligand receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 279 (showing top): BROWNE_HCMV_INFECTION_4HR_UP, GOBP_DIGESTION, GOBP_ACID_SECRETION, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_INFLAMMATORY_RESPONSE, REACTOME_EICOSANOID_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_HEAT_GENERATION, GOBP_POSITIVE_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (10): inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell death (GO:0008219), intestine smooth muscle contraction (GO:0014827), positive regulation of fever generation (GO:0031622), negative regulation of gastric acid secretion (GO:0060455), signal transduction (GO:0007165)

GO Molecular Function (3): prostaglandin E receptor activity (GO:0004957), G protein-coupled receptor activity (GO:0004930), prostaglandin receptor activity (GO:0004955)

GO Cellular Component (3): nuclear envelope (GO:0005635), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Eicosanoid ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
cellular process	2
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
regulation of biological quality	1
phasic smooth muscle contraction	1
gastro-intestinal system smooth muscle contraction	1
fever generation	1
positive regulation of acute inflammatory response	1
regulation of fever generation	1
positive regulation of heat generation	1
gastric acid secretion	1
negative regulation of secretion	1
regulation of gastric acid secretion	1
negative regulation of digestive system process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
prostaglandin receptor activity	1
transmembrane signaling receptor activity	1
prostanoid receptor activity	1
nucleus	1
endomembrane system	1
organelle envelope	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGER3	PTGS2	P35354	802
PTGER3	GNAQ	P50148	760
PTGER3	PTGES	O14684	749
PTGER3	TSNAX	Q99598	737
PTGER3	DISC1	Q9NRI5	706
PTGER3	PTGS1	P23219	699
PTGER3	CDCP1	Q9H5V8	695
PTGER3	PTGER4	P35408	667
PTGER3	PTGES2	Q9H7Z7	651
PTGER3	LTB4R	Q15722	623
PTGER3	GNA12	Q03113	618
PTGER3	IL1B	P01584	607
PTGER3	PTGES3	Q15185	597
PTGER3	LTB4R2	Q9NPC1	591
PTGER3	IL6	P05231	581

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
PTGER3	RGS20	psi-mi:“MI:0915”(physical association)	0.370
PTGER3	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.370
PTGER3	KRT38	psi-mi:“MI:0915”(physical association)	0.370
PTGER3	PTPRF	psi-mi:“MI:0914”(association)	0.350
PTGER3	ECD	psi-mi:“MI:0914”(association)	0.350

BioGRID (238): PTGER3 (Two-hybrid), PTGER3 (Two-hybrid), PTGER3 (Two-hybrid), REL (Two-hybrid), TCF4 (Two-hybrid), RGS20 (Two-hybrid), KRT38 (Two-hybrid), SPRY2 (Two-hybrid), RGS17 (Two-hybrid), EFEMP2 (Two-hybrid), ADAMTSL4 (Two-hybrid), CCDC33 (Two-hybrid), KRT40 (Two-hybrid), MGAT5B (Two-hybrid), TRIM42 (Two-hybrid)

ESM2 similar proteins: A5D7K8, O35932, O95136, O95977, P21731, P30557, P30987, P34972, P34978, P34979, P34980, P35375, P35408, P37289, P43088, P43114, P43115, P43116, P43117, P43118, P43119, P43252, P43253, P46069, P47752, P47901, P47936, P50131, P52592, P56486, P70263, P70597, P79393, Q13258, Q28691, Q28905, Q5R949, Q62053, Q62928, Q8MJ08

Diamond homologs: O02662, P21731, P30557, P30987, P34978, P34979, P34980, P34995, P35375, P37289, P43088, P43115, P43117, P43118, P43119, P43141, P43252, P43253, P46069, P46626, P50131, P56486, P70597, P79393, Q28524, Q28550, Q28905, Q804Q2, Q804X9, Q8R456, Q95125, Q95252, Q9BGL8, Q9QXZ9, Q9TST4, Q9UHM6, Q9XT57, Q9XT58, P32240, P35408

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
“prostaglandin E2”	up-regulates	PTGER3	“chemical activation”
PTGER3	“up-regulates activity”	GNAI1	binding
PTGER3	“up-regulates activity”	GNAI3	binding
PTGER3	“up-regulates activity”	GNAO1	binding
PTGER3	“up-regulates activity”	GNAZ	binding
PTGER3	“up-regulates activity”	GNA12	binding
“prostaglandin E2(1-)”	“up-regulates activity”	PTGER3	“chemical activation”
PTGER3	“up-regulates quantity”	EGFR	relocalization
PTGER3	“up-regulates activity”	SRC	binding
PTGER3	up-regulates	GNAI1	binding
PTGER3	up-regulates	GNB3	binding
PTGER3	up-regulates	GNG12	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1060 predictions. Top by Δscore:

Variant	Effect	Δscore
1:70971653:AT:A	donor_gain	1.0000
1:71012485:C:CC	acceptor_gain	1.0000
1:71012337:A:C	donor_gain	0.9900
1:71012481:TTAT:T	acceptor_gain	0.9900
1:71012482:TAT:T	acceptor_gain	0.9900
1:71012484:TCTAA:T	acceptor_loss	0.9900
1:71012485:C:CA	acceptor_loss	0.9900
1:71012486:T:G	acceptor_loss	0.9900
1:71046679:A:AC	donor_gain	0.9900
1:71046679:ACCA:A	donor_loss	0.9900
1:71046680:C:CC	donor_gain	0.9900
1:71046680:C:CT	donor_loss	0.9900
1:70971654:T:C	donor_gain	0.9800
1:70971654:T:TA	donor_gain	0.9800
1:70974389:C:CC	acceptor_gain	0.9800
1:71012480:ATTAT:A	acceptor_gain	0.9800
1:70974384:CTGAT:C	acceptor_gain	0.9700
1:70974386:GAT:G	acceptor_gain	0.9700
1:70974289:AATCT:A	donor_loss	0.9500
1:70974290:ATCTC:A	donor_loss	0.9500
1:70974291:TCTCA:T	donor_loss	0.9500
1:70974292:CTCAC:C	donor_loss	0.9500
1:70974293:TCA:T	donor_loss	0.9500
1:70974294:CACCT:C	donor_loss	0.9500
1:70974295:A:C	donor_loss	0.9500
1:70974296:C:A	donor_loss	0.9500
1:71012483:AT:A	acceptor_gain	0.9500
1:71012317:T:A	donor_gain	0.9400
1:71041456:CATCA:C	acceptor_gain	0.9400
1:71041459:C:CT	acceptor_gain	0.9400

AlphaMissense

2510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:71047131:G:C	S149R	0.997
1:71047131:G:T	S149R	0.997
1:71047133:T:G	S149R	0.997
1:71046951:G:C	F209L	0.996
1:71046951:G:T	F209L	0.996
1:71046953:A:G	F209L	0.996
1:71047218:C:A	W120C	0.996
1:71047218:C:G	W120C	0.996
1:71046955:C:G	C208S	0.995
1:71046956:A:G	C208R	0.995
1:71046956:A:T	C208S	0.995
1:71046959:A:G	W207R	0.995
1:71046959:A:T	W207R	0.995
1:71047177:C:T	G134E	0.995
1:71046954:G:C	C208W	0.994
1:71046957:C:A	W207C	0.994
1:71046957:C:G	W207C	0.994
1:71047178:C:A	G134W	0.994
1:71012352:A:G	W344R	0.993
1:71012352:A:T	W344R	0.993
1:71012378:G:T	A335D	0.993
1:71047314:G:C	F88L	0.993
1:71047314:G:T	F88L	0.993
1:71047316:A:G	F88L	0.993
1:71047380:G:C	N66K	0.993
1:71047380:G:T	N66K	0.993
1:71046695:A:G	W295R	0.992
1:71046695:A:T	W295R	0.992
1:71046952:A:C	F209C	0.992
1:71046955:C:T	C208Y	0.992

dbSNP variants (sampled 300 via entrez): RS1000031976 (1:70950671 A>G), RS1000034830 (1:71008387 T>A), RS1000042859 (1:71016244 C>T), RS1000087594 (1:70936616 T>G), RS1000089240 (1:70944824 G>T), RS1000116575 (1:70930261 C>T), RS1000119724 (1:70983799 G>A), RS1000128630 (1:71040486 G>A), RS1000137160 (1:70933026 T>G), RS1000167446 (1:70928804 A>G), RS1000182057 (1:70872789 T>C), RS1000205432 (1:70914893 T>C), RS1000217921 (1:70929011 G>A), RS1000231314 (1:71033553 T>C), RS1000264715 (1:71001767 G>A)

Disease associations

OMIM: gene MIM:176806 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002701_19	Verbal declarative memory	2.000000e-06
GCST005316_297	Intelligence (MTAG)	3.000000e-08
GCST009267_17	Dental caries (decayed, missing and filled teeth)	3.000000e-06
GCST012203_1	Colon cancer	1.000000e-08
GCST012206_4	Proximal colorectal cancer	1.000000e-08
GCST012336_1	Alcohol use disorder (consumption score)	2.000000e-06
GCST90006994_11	Gut microbiota relative abundance (Ruminococcus belonging to family Erysipelotrichaceae)	1.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0006806	paragraph delayed recall measurement
EFO:0004337	intelligence
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009458	alcohol use disorder measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363068 (PROTEIN FAMILY), CHEMBL3710 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 21,038 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL426559	LAROPIPRANT	4	541
CHEMBL494	ILOPROST	4	234
CHEMBL548	DINOPROSTONE	4	14,939
CHEMBL815	DINOPROST	4	3,118
CHEMBL3301604	RALINEPAG	3	260
CHEMBL4297633	SEPETAPROST	3	100
CHEMBL1201379	FLUPROSTENOL	2	1,846
CHEMBL2220404	CLOPROSTENOL	2

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11209716	Toxicity	3	Ace Inhibitors;Plain	Cough;Hypertension
rs7551789	Toxicity	3	aspirin	Asthma

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs959	PTGER3		0.00	0
rs7543182	PTGER3		0.00	0
rs7551789	PTGER3	3	1.50	1	aspirin
rs11209716	PTGER3	3	2.50	1	Ace Inhibitors;Plain

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Prostanoid receptors

Most potent curated ligand interactions (43 total), top 25:

Ligand	Action	Affinity	Parameter
SC46275	Full agonist	11.0	pIC50
DG-041	Antagonist	10.1	pKi
MB-28767	Full agonist	9.85	pKi
ONO-AE5-599	Antagonist	9.72	pIC50
L-798,106	Antagonist	9.68	pKi
ONO-AE3-240	Antagonist	9.6	pKi
[3H]PGE2	Full agonist	9.5	pKd
PGE1	Full agonist	9.0	pKi
sulprostone	Full agonist	8.85	pEC50
11-deoxy-PGE1	Partial agonist	8.82	pKi
16,16-dimethyl-PGE2	Partial agonist	8.72	pKi
PGE2	Full agonist	8.68	pKd
17-phenyl-ω-trinor-PGE2	Full agonist	8.43	pKi
L-826266	Antagonist	8.35	pKB
GR 63799	Agonist	8.32	pKi
misoprostol (free acid form)	Full agonist	8.1	pKi
ONO-AP-324	Partial agonist	7.96	pKi
enprostil	Full agonist	7.92	pKi
carbacyclin	Full agonist	7.85	pKi
STA2	Full agonist	7.64	pKi
ONO-AE3-208	Antagonist	7.52	pKi
isocarbacyclin	Full agonist	7.51	pKi
PGF2α	Full agonist	7.42	pKi
rivenprost	Partial agonist	7.25	pKi
ONO-8711	Antagonist	7.17	pKi

Binding affinities (BindingDB)

48 measured of 69 human assays (71 total across all organisms); most potent 48 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_5311503	KI	0.3 nM
NSC_3080928	KI	0.4 nM
CAS_41598-07-6	KI	1.7 nM
6-(1-ethyl-4-fluoroindazol-6-yl)-3-[(3R)-3-methyl-2-oxopiperidin-3-yl]-1H-pyridin-2-one	KI	2 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(R)-3-(3-Methyl-2-oxopiperidin-3-yl)-6-(5-methylquinolin-3-yl)pyridin-2(1H)-one	KI	3.3 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
6-(4-chloro-1-methylindazol-6-yl)-3-[(3R)-3-methyl-2-oxopiperidin-3-yl]-1H-pyridin-2-one	KI	3.6 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(Z)-7-[(1R,4S,5R)-4-hydroxy-5-[(E,3S)-3-hydroxyoct-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-enoic acid	EC50	4.6 nM	US-9156810: Treatment of inflammatory bowel disease
(R)-6-(5-Ethylquinolin-7-yl)-3-(3-methyl-2-oxopiperidin-3-yl)pyridin-2(1H)-one	KI	4.6 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
(R)-3-(3-Methyl-2-oxopiperidin-3-yl)-6-(5-methylquinolin-7-yl)pyridin-2(1H)-one	KI	7.2 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
(R)-6-(5-Cyclopropylquinolin-7-yl)-3-(3-methyl-2-oxopiperidin-3-yl)pyridin-2(1H)-one	KI	7.3 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
6-(7-chloro-1-methylbenzimidazol-5-yl)-3-[(3R)-3-methyl-2-oxopiperidin-3-yl]-1H-pyridin-2-one	KI	7.8 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(R)-6-(5-Chloroquinolin-7-yl)-3-(3-methyl-2-oxopiperidin-3-yl)pyridin-2(1H)-one	KI	8.9 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
(3R)-3-[6-(1-ethyl-4-methylindazol-6-yl)-2-oxopiperidin-3-yl]-3-methylpiperidin-2-one	KI	9.5 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
4-[[6-(4-hydroxypiperidin-1-yl)-3-methylpyridine-2-carbonyl]amino]-3,5-dimethylbenzoic acid	IC50	9.8 nM	US-8933099: Monocyclic pyridine derivative
4-[2-[(1R,2R)-2-[(E)-4-(3-fluorophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	10 nM	US-9394273: Therapeutic prostaglandin receptor agonists
4-[2-[(1R,2R)-2-[(E)-4-(2,5-difluorophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	10 nM	US-9394273: Therapeutic prostaglandin receptor agonists
7-[(1R,4S,5R)-4-hydroxy-5-[(E,3S)-3-hydroxyoct-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-ynoic acid	EC50	11 nM	US-9156810: Treatment of inflammatory bowel disease
4-[2-[(1R,2R)-2-[(E)-4-(4-fluorophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	11 nM	US-9394273: Therapeutic prostaglandin receptor agonists
(3R)-3-methyl-3-[6-(1-methylindol-6-yl)-2-oxopiperidin-3-yl]piperidin-2-one	KI	11.2 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
6-(7-fluoro-1-methylindol-5-yl)-3-[(3R)-3-methyl-2-oxopyrrolidin-3-yl]piperidin-2-one	KI	11.9 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(3R)-3-methyl-3-[6-(1-methylindol-5-yl)-2-oxopiperidin-3-yl]piperidin-2-one	KI	12.2 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(3R)-3-[6-(4-fluoro-1-methylindazol-6-yl)-2-oxopiperidin-3-yl]-3-methylpiperidin-2-one	KI	13.9 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
6-(4-chloro-1-methylindazol-6-yl)-3-[(3R)-3-methyl-2-oxopyrrolidin-3-yl]piperidin-2-one	KI	14.2 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(R)-3-(3-Methyl-2-oxopyrrolidin-3-yl)-6-(5-methylquinolin-3-yl)pyridin-2(1H)-one	KI	18.6 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
6-(1-ethylindol-6-yl)-3-[(3R)-3-methyl-2-oxopyrrolidin-3-yl]piperidin-2-one	KI	19.9 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(3R)-3-[6-(1,4-dimethylindazol-6-yl)-2-oxopiperidin-3-yl]-3-methylpiperidin-2-one	KI	25 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
4-[2-[(1R,2R)-2-[(E)-4-(3-bromophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	26 nM	US-9394273: Therapeutic prostaglandin receptor agonists
6-(3-cyclopropyl-7-fluoro-2H-indazol-5-yl)-3-[(3R)-3-methyl-2-oxopiperidin-3-yl]-3H-pyridin-2-one	KI	29.2 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
4-[2-[(1R,2R)-2-[(E)-4-(3,4-difluorophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	30 nM	US-9394273: Therapeutic prostaglandin receptor agonists
6-(1-ethyl-4-methylindazol-6-yl)-3-[(3R)-3-methyl-2-oxopyrrolidin-3-yl]-1H-pyridin-2-one	KI	31.6 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
6-(1-methylindol-5-yl)-3-[(3R)-3-methyl-2-oxopyrrolidin-3-yl]piperidin-2-one	KI	46 nM	US-9278953: Antagonists of prostaglandin EP3 receptor
(R)-3-(6-(5-fluoroquinolin-7-yl)-2-hydroxypyridin-3-yl)-3-methylpiperidin-2-one	KI	48.6 nM	US-9738626: Antagonists of prostaglandin EP3 receptor
4-[2-[(1R,2R)-2-[(E)-4-(2-fluorophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	76 nM	US-9394273: Therapeutic prostaglandin receptor agonists
PGI2	KI	132 nM
4-[2-[(1R,2R)-2-[(E)-4-(2,3-difluorophenyl)-3-hydroxybut-1-enyl]-5-oxocyclopentyl]ethyl]benzoic acid	EC50	164 nM	US-9394273: Therapeutic prostaglandin receptor agonists
methyl (Z)-7-[(1R,4S,5R)-4-hydroxy-5-[(E,3S)-3-hydroxyoct-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-enoate	EC50	531 nM	US-9156810: Treatment of inflammatory bowel disease
methyl 7-[(1R,4S,5R)-4-hydroxy-5-[(E,3S)-3-hydroxyoct-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-ynoate	EC50	559 nM	US-9156810: Treatment of inflammatory bowel disease
(Z)-7-[(1R,4S,5R)-4-hydroxy-5-[(E)-3-hydroxy-4-phenylbut-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-enoic acid	EC50	589 nM	US-9156810: Treatment of inflammatory bowel disease
CAS_54751	KI	697 nM
(Z)-7-[(1R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid	KI	861 nM
ILOPROST	KI	1040 nM
CAS_94079-80-8	KI	1340 nM
CAS_33458-93-4	KI	1420 nM
(Z)-7-[(1R,4S,5R)-4-hydroxy-5-[(E)-3-hydroxy-5-phenylpent-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-enoic acid	EC50	1860 nM	US-9156810: Treatment of inflammatory bowel disease
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
U46619	KI	3970 nM
(Z)-7-[(1R,4S,5R)-5-[(E)-4-(1-benzothiophen-2-yl)-3-hydroxybut-1-enyl]-4-hydroxy-3,3-dimethyl-2-oxocyclopentyl]hept-5-enoic acid	IC50	4700 nM	US-9156810: Treatment of inflammatory bowel disease
methyl (Z)-7-[(1R,4S,5R)-4-hydroxy-5-[(E)-3-hydroxy-5-phenylpent-1-enyl]-3,3-dimethyl-2-oxocyclopentyl]hept-5-enoate	IC50	6610 nM	US-9156810: Treatment of inflammatory bowel disease

ChEMBL bioactivities

1186 potent at pChembl≥5 of 1216 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL1093897
9.70	IC50	0.2	nM	CHEMBL465122
9.70	IC50	0.2	nM	CHEMBL1090501
9.70	IC50	0.2	nM	CHEMBL1088780
9.70	IC50	0.2	nM	CHEMBL1089094
9.70	IC50	0.2	nM	CHEMBL1089095
9.70	IC50	0.2	nM	CHEMBL1093239
9.70	IC50	0.2	nM	CHEMBL1093843
9.70	IC50	0.2	nM	CHEMBL1090112
9.52	IC50	0.3	nM	CHEMBL464032
9.52	IC50	0.3	nM	CHEMBL519598
9.52	IC50	0.3	nM	CHEMBL1090460
9.52	IC50	0.3	nM	CHEMBL1093559
9.52	IC50	0.3	nM	CHEMBL1090222
9.52	IC50	0.3	nM	CHEMBL1088815
9.52	IC50	0.3	nM	CHEMBL1092871
9.48	Ki	0.33	nM	DINOPROSTONE
9.47	EC50	0.34	nM	CHEMBL3889508
9.40	Ki	0.4	nM	CHEMBL5092858
9.40	IC50	0.4	nM	CHEMBL1091164
9.40	IC50	0.4	nM	CHEMBL1089454
9.40	IC50	0.4	nM	CHEMBL1088822
9.40	IC50	0.4	nM	CHEMBL1088848
9.40	IC50	0.4	nM	CHEMBL1091146
9.30	IC50	0.5	nM	CHEMBL479434
9.30	Ki	0.5	nM	CHEMBL5086191
9.30	IC50	0.5	nM	CHEMBL1089161
9.30	IC50	0.5	nM	CHEMBL1089491
9.30	IC50	0.5	nM	CHEMBL1092230
9.30	IC50	0.5	nM	CHEMBL1088823
9.22	Ki	0.6	nM	CHEMBL217991
9.22	Ki	0.6	nM	CHEMBL218071
9.22	IC50	0.6	nM	CHEMBL1090459
9.22	IC50	0.6	nM	CHEMBL1089455
9.22	IC50	0.6	nM	CHEMBL1088846
9.22	IC50	0.6	nM	CHEMBL1093790
9.22	IC50	0.6	nM	CHEMBL1093125
9.15	Ki	0.7	nM	CHEMBL217941
9.15	EC50	0.7	nM	CHEMBL3751951
9.15	IC50	0.7	nM	CHEMBL465947
9.15	IC50	0.7	nM	CHEMBL466184
9.15	IC50	0.7	nM	CHEMBL1090113
9.15	IC50	0.7	nM	CHEMBL1091145
9.10	EC50	0.8	nM	CHEMBL3804978
9.10	EC50	0.8	nM	CHEMBL4217198
9.05	EC50	0.89	nM	CHEMBL3967903
9.05	Ki	0.9	nM	CHEMBL217941
9.05	IC50	0.9	nM	CHEMBL1090507
9.05	IC50	0.9	nM	CHEMBL1093124
9.05	IC50	0.9	nM	CHEMBL1088847

PubChem BioAssay actives

1126 with measured affinity, of 1684 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
(E)-N-(3-chlorophenyl)sulfonyl-3-[3,3-difluoro-1-(naphthalen-2-ylmethyl)-2-oxoindol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0001	uM
2-[[3-(2,4-dichlorophenyl)sulfanyl-1H-indol-4-yl]oxy]-N-(4,5-dichlorothiophen-2-yl)sulfonylacetamide	410487: Displacement of [3H]PGE2 from human EP3 receptor in presence of 10% human serum	ic50	0.0002	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-2-oxo-3H-indol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3,3-difluoro-2-oxoindol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3,3-difluoro-2-oxoindol-7-yl]-N-(3,4-difluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3,3-difluoro-2-oxoindol-7-yl]-N-(3,4-dichlorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(E)-N-(3-chlorophenyl)sulfonyl-3-[1-[(2,4-dichlorophenyl)methyl]-3,3-difluoro-2-oxoindol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3,3-difluoro-2-oxoindol-7-yl]-N-(4-fluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(E)-3-[3,3-difluoro-1-(naphthalen-2-ylmethyl)-2-oxoindol-7-yl]-N-(3,4-difluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0002	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]cyclopentyl]-N-methylsulfonylhept-5-enamide	1331418: Agonist activity at human EP3 receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0003	uM
2-[[3-(3,4-dichlorophenyl)sulfanyl-1H-indol-4-yl]oxy]-N-(4,5-dichlorothiophen-2-yl)sulfonylacetamide	410497: Antagonist activity at human EP3 receptor assessed as cAMP production by cell-based assay	ic50	0.0003	uM
N-(4,5-dichlorothiophen-2-yl)sulfonyl-2-[(3-naphthalen-2-ylsulfanyl-1H-indol-4-yl)oxy]acetamide	410487: Displacement of [3H]PGE2 from human EP3 receptor in presence of 10% human serum	ic50	0.0003	uM
(E)-3-[1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0003	uM
(E)-N-(3,4-dichlorophenyl)sulfonyl-3-[1-[(3,4-difluorophenyl)methyl]-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0003	uM
(E)-3-[3-methyl-1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0003	uM
(E)-3-[3,3-difluoro-1-(naphthalen-2-ylmethyl)-2-oxoindol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0003	uM
(E)-N-(3,4-dichlorophenyl)sulfonyl-3-[3,3-difluoro-1-(naphthalen-2-ylmethyl)-2-oxoindol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0003	uM
dinoprostone	308195: Displacement of [3H]PGE2 from human EP3 receptor expressed in HEK293 cells	ki	0.0003	uM
1-(4,5-dichlorothiophen-2-yl)sulfonyl-3-[(2E)-2-[1-[4-(trifluoromethyl)phenyl]-5,6-dihydro-4H-indazol-7-ylidene]ethyl]urea	1808180: Displacement of [3H]-PGE2 from human EP3 receptor assessed as inhibition constant incubated for 2 hrs by TopCount scintillation counting method	ki	0.0004	uM
(E)-N-(3,4-difluorophenyl)sulfonyl-3-[1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0004	uM
(E)-N-(3-chlorophenyl)sulfonyl-3-[1-[(3,4-difluorophenyl)methyl]-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0004	uM
(E)-N-(4,5-dichlorothiophen-2-yl)sulfonyl-3-[1-[(3,4-difluorophenyl)methyl]-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0004	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-3H-indol-7-yl]-N-(3,4-difluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0004	uM
(E)-N-(3-chlorophenyl)sulfonyl-3-[3-methyl-1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0004	uM
1-[(2E)-2-[1-[(2,4-dichlorophenyl)methyl]-5,6-dihydro-4H-indazol-7-ylidene]ethyl]-3-(4,5-dichlorothiophen-2-yl)sulfonylurea	1808180: Displacement of [3H]-PGE2 from human EP3 receptor assessed as inhibition constant incubated for 2 hrs by TopCount scintillation counting method	ki	0.0005	uM
N-(4,5-dichlorothiophen-2-yl)sulfonyl-2-[[3-(4-methoxyphenyl)sulfanyl-1H-indol-4-yl]oxy]acetamide	410486: Displacement of [3H]PGE2 from human EP3 receptor	ic50	0.0005	uM
(E)-N-(3-chlorophenyl)sulfonyl-3-[1-[(2,4-dichlorophenyl)methyl]-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0005	uM
(E)-N-(3,4-dichlorophenyl)sulfonyl-3-[1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0005	uM
(E)-N-(3-chlorophenyl)sulfonyl-3-[1-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0005	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-3H-indol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0005	uM
(E)-3-[2-[(6-phenylmethoxynaphthalen-2-yl)methyl]phenyl]-N-thiophen-2-ylsulfonylprop-2-enamide	276202: Binding affinity to EP3 receptor	ki	0.0006	uM
(E)-N-(5-bromo-2-methoxyphenyl)sulfonyl-3-[2-(naphthalen-2-ylmethyl)phenyl]prop-2-enamide	276202: Binding affinity to EP3 receptor	ki	0.0006	uM
(E)-N-(3-chlorophenyl)sulfonyl-3-[1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0006	uM
(E)-N-(3,4-difluorophenyl)sulfonyl-3-[3-methyl-1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0006	uM
(E)-3-[1-(naphthalen-2-ylmethyl)-2,3-dioxoindol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0006	uM
(E)-N-(3,4-dichlorophenyl)sulfonyl-3-[3-methyl-1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0006	uM
(E)-3-[3-hydroxy-1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0006	uM
2-[2-[(4S)-4-[(E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxyprop-1-enyl]-2-oxo-1,3-oxazolidin-3-yl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid	1372358: Agonist activity at recombinant human EP3 receptor expressed in CHO cells assessed as increase in intracellular calcium level measured at 3 secs time interval by fura-2-AM dye based fluorescence assay	ec50	0.0007	uM
(E)-N-(5-bromo-2-methoxyphenyl)sulfonyl-3-[2-[(6-phenylmethoxynaphthalen-2-yl)methyl]phenyl]prop-2-enamide	276221: Binding affinity to EP3 receptor in presence of HSA	ki	0.0007	uM
N-(3,4-difluorophenyl)sulfonyl-2-[(3-naphthalen-2-ylsulfanyl-1H-indol-4-yl)oxy]acetamide	410487: Displacement of [3H]PGE2 from human EP3 receptor in presence of 10% human serum	ic50	0.0007	uM
N-(4-methoxyphenyl)sulfonyl-2-[(3-naphthalen-2-ylsulfanyl-1H-indol-4-yl)oxy]acetamide	410486: Displacement of [3H]PGE2 from human EP3 receptor	ic50	0.0007	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-2-oxo-3H-indol-7-yl]-N-(3,4-difluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0007	uM
(E)-3-[1-[(3,4-difluorophenyl)methyl]-2-oxo-3H-indol-7-yl]-N-(2,4,5-trifluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0007	uM
2-[(2R,4aR,5R,6R,7aS)-6-hydroxy-5-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]-1,3-thiazole-4-carboxylic acid	1300199: Agonist activity at human EP3 receptor expressed in CHO cells assessed as increase in intracellular calcium level by fluorescence based analysis	ec50	0.0008	uM
2-[2-[(1R,2R)-2-[(E,4S)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopentyl]ethylsulfanyl]-1,3-thiazole-4-carboxylic acid	1372358: Agonist activity at recombinant human EP3 receptor expressed in CHO cells assessed as increase in intracellular calcium level measured at 3 secs time interval by fura-2-AM dye based fluorescence assay	ec50	0.0008	uM
(Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-5-oxocyclopentyl]hept-5-enoic acid	1331418: Agonist activity at human EP3 receptor expressed in CHO cells assessed as increase in intracellular calcium level by Fura 2-AM dye based fluorescence assay	ec50	0.0009	uM
(E)-3-[1-[(3,4-difluorophenyl)methyl]-2-oxo-3H-indol-7-yl]-N-(3,4-difluorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0009	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-3-methyl-2-oxo-3H-indol-7-yl]-N-(3,4-dichlorophenyl)sulfonylprop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0009	uM
(E)-N-(4-fluorophenyl)sulfonyl-3-[3-hydroxy-1-(naphthalen-2-ylmethyl)-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0009	uM
(E)-N-(3,4-dichlorophenyl)sulfonyl-3-[1-[(3,4-difluorophenyl)methyl]-3-methyl-2-oxo-3H-indol-7-yl]prop-2-enamide	475924: Displacement of [3H]PGE2 from human EP3 receptor in buffer	ic50	0.0009	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
Estradiol	affects expression, affects binding, increases expression, increases reaction	3
bisphenol A	increases expression	2
nickel sulfate	decreases expression	2
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
diethyl phthalate	affects reaction, affects cotreatment, affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
diisononyl phthalate	affects expression, affects reaction, affects cotreatment	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
tetramethylpyrazine	affects cotreatment, decreases expression	1
diisobutyl phthalate	affects cotreatment, affects expression, affects reaction	1
benzo(e)pyrene	increases methylation	1
butylbenzyl phthalate	affects reaction, affects cotreatment, affects expression	1
ciglitazone	affects cotreatment, decreases expression	1
evodiamine	affects cotreatment, decreases expression	1
rofecoxib	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
fatostatin	decreases expression	1
Sunitinib	increases expression	1
Terbinafine	increases expression, increases reaction, increases response to substance, decreases reaction	1
Allergens	increases expression, decreases expression, decreases reaction, increases abundance	1
Aspirin	affects response to substance	1
Vehicle Emissions	decreases reaction, increases abundance, increases expression	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	increases expression	1
Dibutyl Phthalate	affects cotreatment, affects expression, affects reaction	1

ChEMBL screening assays

194 unique, capped per target: 140 binding, 51 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009658	Binding	Inhibition of EP3 receptor by FLIPR assay	Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain. — Bioorg Med Chem Lett
CHEMBL1023733	Functional	Antagonist activity at human EP3 receptor expressed in CHO-K1 cells assessed as reversal of inhibition of forskolin-induced cAMP production	Peri-substituted hexahydro-indolones as novel, potent and selective human EP3 receptor antagonists. — Bioorg Med Chem Lett
CHEMBL4005284	ADMET	Displacement of [3H]-PGE2 from recombinant human EP3v6 receptor expressed in HEK293 cell membranes incubated for 1 hr by top count scintillation counting method	Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2CM	Abcam HeLa PTGER3 KO	Cancer cell line	Female
CVCL_KV68	cAMP Hunter CHO-K1 PTGER3 Gi	Spontaneously immortalized cell line	Female
CVCL_KY88	PathHunter CHO-K1 PTGER3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_TH50	HAP1 PTGER3 (-) 1	Cancer cell line	Male
CVCL_TH51	HAP1 PTGER3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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