PTGER4

gene
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Also known as EP4

Summary

PTGER4 (prostaglandin E receptor 4, HGNC:9596) is a protein-coding gene on chromosome 5p13.1, encoding Prostaglandin E2 receptor EP4 subtype (P35408). 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 can activate T-cell factor signaling. It has been shown to mediate PGE2 induced expression of early growth response 1 (EGR1), regulate the level and stability of cyclooxygenase-2 mRNA, and lead to the phosphorylation of glycogen synthase kinase-3. Knockout studies in mice suggest that this receptor may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses.

Source: NCBI Gene 5734 — RefSeq curated summary.

At a glance

  • GWAS associations: 29
  • Clinical variants (ClinVar): 77 total
  • Druggable target: yes — 9 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000958

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:9596
Approved symbolPTGER4
Nameprostaglandin E receptor 4
Location5p13.1
Locus typegene with protein product
StatusApproved
AliasesEP4
Ensembl geneENSG00000171522
Ensembl biotypeprotein_coding
OMIM601586
Entrez5734

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000302472, ENST00000509543, ENST00000512578, ENST00000513635, ENST00000514343, ENST00000963428

RefSeq mRNA: 1 — MANE Select: NM_000958 NM_000958

CCDS: CCDS3930

Canonical transcript exons

ENST00000302472 — 3 exons

ExonStartEnd
ENSE000011432024069177940693735
ENSE000011432134068095140681860
ENSE000020247514067991540680478

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.1792 / max 880.8595, expressed in 1433 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter IDTPM avgSamples expressed
5623022.99241361
562320.9865120
562270.8471332
562330.6239219
562280.2674117
562290.2565106
562310.178357
2035350.027011

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
palpebral conjunctivaUBERON:000181298.94gold quality
jejunal mucosaUBERON:000039998.00gold quality
renal glomerulusUBERON:000007497.72gold quality
mucosa of sigmoid colonUBERON:000499397.46gold quality
metanephric glomerulusUBERON:000473697.31gold quality
bronchial epithelial cellCL:000232896.91gold quality
colonic mucosaUBERON:000031796.73gold quality
visceral pleuraUBERON:000240195.71gold quality
synovial jointUBERON:000221795.65gold quality
pleuraUBERON:000097795.55gold quality
germinal epithelium of ovaryUBERON:000130495.38gold quality
epithelium of bronchusUBERON:000203195.31gold quality
parietal pleuraUBERON:000240095.31gold quality
bronchusUBERON:000218595.14gold quality
superficial temporal arteryUBERON:000161494.87gold quality
jejunumUBERON:000211594.04gold quality
lower lobe of lungUBERON:000894993.81gold quality
mammary ductUBERON:000176593.49gold quality
mucosa of urinary bladderUBERON:000125993.47gold quality
vena cavaUBERON:000408793.31gold quality
duodenumUBERON:000211493.30gold quality
skin of hipUBERON:000155493.05gold quality
trabecular bone tissueUBERON:000248393.03gold quality
epithelium of mammary glandUBERON:000324492.66gold quality
granulocyteCL:000009492.34gold quality
mucosa of paranasal sinusUBERON:000503091.93gold quality
leukocyteCL:000073891.44gold quality
layer of synovial tissueUBERON:000761691.40gold quality
mononuclear cellCL:000084291.23gold quality
bone marrowUBERON:000237191.11gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

ExperimentMarker?Max mean expression
E-CURD-46yes45.44
E-CURD-88yes39.78
E-CURD-122yes36.58
E-CURD-77no608.36
E-MTAB-5061no4.29
E-ANND-3no0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, FOXC1, HOXA10, NFKB1, PPARD, RELA, SNAI1, SP1, STAT3, TCF3, TFAP2A, XBP1

miRNA regulators (miRDB)

115 targeting PTGER4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-8485100.0077.574731
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-4533100.0069.482758
HSA-MIR-4510100.0066.602050
HSA-MIR-6127100.0066.762188
HSA-MIR-6129100.0066.462080
HSA-MIR-6130100.0066.692012
HSA-MIR-6133100.0066.482064
HSA-MIR-5692A100.0074.406850
HSA-MIR-428299.9975.366408
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-32-5P99.9875.211964
HSA-MIR-92A-3P99.9875.211960
HSA-MIR-92B-3P99.9875.251955
HSA-MIR-25-3P99.9874.601817
HSA-MIR-363-3P99.9874.721821
HSA-MIR-367-3P99.9874.831819
HSA-MIR-4789-5P99.9870.762721
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-3065-5P99.9771.563281
HSA-MIR-1229-3P99.9766.49906
HSA-MIR-590-3P99.9674.346478
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753

Literature-anchored findings (GeneRIF, showing 40)

  • Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. (PMID:11782353)
  • Placentally derived prostaglandin E2 acts via the EP4 receptor to inhibit IL-2-dependent proliferation of CTLL-2 T cells. (PMID:11876748)
  • Increased PGE(2) synthesis in the adjacent stroma and its biological effect via EP(4) on the carcinoma cells may contribute to tumor growth and progression of gallbladder carcinoma. (PMID:11948128)
  • effects of PGE2 on monocyte-derived dendritic cells were mediated through increased cyclic adenosine monophosphate by 2 of the known PGE2 receptors, EP2 and EP4 (PMID:12149218)
  • endogenous PGE(2) may modulate inflammation during atherogenesis and other inflammatory diseases by suppressing macrophage-derived chemokine production via the EP4 receptor (PMID:12215436)
  • Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth inhibition in human gastric carcinoma cell lines. (PMID:12228765)
  • activation of PI3K/ERK signaling by the EP(4) receptors induces the functional expression of early growth response factor-1 (EGR-1). (PMID:12566441)
  • COX-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, EP2 receptor, and EP4 receptor (PMID:14517215)
  • both beta-arrestin1 recruitment and the presence of Ser/Thr residues in the distal half of the C-terminal domain were necessary for maximal agonist-induced internalization (PMID:14709160)
  • Vascular COX-2 was colocalized with prostaglandin E(2) EP4 receptors but not with EP2 receptors in kidney (PMID:15100359)
  • 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)
  • Endothelin-1-induced prostaglandin E2-EP2 and EP4 signaling regulates vascular endothelial growth factor production and ovarian carcinoma cell invasion (PMID:15347673)
  • Prostaglandin (PG)E2 induces an increase in intracellular cyclic AMP concentration in the T-leukemic cell line Jurkat via the E-prostanoid (EP)3 receptor. (PMID:15528329)
  • PGE2 increases VEGF transcriptionally and involves the Sp-1 binding site via a cAMP-dependent mechanism involving EP2 and EP4 receptors (PMID:15970595)
  • EP4 overexpression is associated with enhanced inflammatory reaction in atherosclerotic plaques (PMID:16020747)
  • We concluded that PGE2 stimulates the BNP promoter mainly via EP4, PKA, Rap, and p42/44 MAPK. (PMID:16428339)
  • seminal plasma and PGE(2) can promote the expression of tumorigenic and angiogenic factors, in cervical adenocarcinoma cells via the EP4 receptor, EGFR, and ERK1/2 signaling pathways (PMID:16574793)
  • Presumably plays a key role for active patency of the human ductus arteriosus in the third trimester. (PMID:16857763)
  • The EP4 receptor mediates IL-1 beta-induced catabolic metabolism via the p38 MAP kinase pathway in human tendon fibroblasts and may play a major role in the tendon’s degenerative changes often seen in the later stages of tendinopathy. (PMID:17046175)
  • Elevated activity in colorectal cancer cells increases resistance to spontaneous apoptosis and promotes anchorage-independent growth, but has no effect on proliferation. (PMID:17130837)
  • EP4 mRNA was significantly higher in normal colon tissue compared with tumor tissue. (PMID:17290397)
  • Genetic variants associated with Crohn disease risk in a locus modulating cis-acting regulatory elements of PTGER4. (PMID:17447842)
  • participates in placentation through EVT invasion by up-regulating PGE2 production and PGE2 receptor expression in first trimester extravillous trophoblasts (PMID:17525067)
  • Results show co-expression of cyclooxygenase-2 and prostaglandin E2 receptors EP1, 2 and 4 in non-small cell lung cancer cells concomitant with the synthesis of PGE2. (PMID:17611676)
  • Results reveal that egr-1 is a target gene of PGE(2) in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. (PMID:17631291)
  • 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)
  • herpes simplex virus type 1 infected mature monocyte-derived dendritic cells demonstrated a dramatic down-regulation of the expression of the EP2 and EP4 receptors (PMID:18086382)
  • mRNA expressions of EP4 receptors observed in NCI-H292 cells and human nasal epithelial cells. (PMID:18254372)
  • PGE(2)-EP4 signaling augments NF-kappaB1 p105 protein stability through EPRAP after proinflammatory stimulation, limiting macrophage activation. (PMID:18270204)
  • CCR7 and the EP2/EP4 receptor signaling pathway are down-stream targets for COX-2 to enhance the migration of breast cancer cells toward LECs and to promote lymphatic invasion (PMID:18319253)
  • Of the 4 EP receptor subtypes, smooth muscle cells in the human pulmonary vein express the EP4 and EP1 receptor subtypes. The relaxations induced by PGE2 in this vessel result from the activation of the EP4 receptor. (PMID:18516068)
  • level of exptression in nasal polyps reversely correlates with chronic rhinosinusitis associated with bronchial asthma (PMID:18797183)
  • The catabolic effects of prostaglandin E2 in osteoarthritis (OA) are specifically mediated via engagement of the EP4 receptor; of the four PGE2 receptors, only EP4 is up-regulated in OA vs normal cartilage. (PMID:18802112)
  • PGE(2) induces angiogenesis in prostate cancer through EP2 and EP4. (PMID:18829529)
  • EP4 is directly involved in regulation of proliferation and invasion of inflammatory breast cancer cells (PMID:19227010)
  • PGE2 acts via prostaglandin receptor EP2- and EP4-mediated signaling and cyclic AMP pathways to up-regulate IL-23 and IL-1 receptor expression. (PMID:19273625)
  • EP2 and EP4 receptor inhibition induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms (PMID:19407222)
  • PGE(2)-stimulated production of Abeta involves EP(4) receptor-mediated endocytosis of PS-1 followed by activation of the gamma-secretase, as well as EP(2) receptor-dependent activation of adenylate cyclase and PKA (PMID:19407341)
  • These results suggest that IL-1beta induces EP4 receptor expression in chondrocytes by an autocrine mechanism that increases PGE2 production, whereas it reduces the expression of EP1 and EP2 via direct action. (PMID:19444759)
  • The EP4 agonist PF-04475270 is a novel ocular hypotensive compound which is bioavailable following topical dosing and effectively lowers intraocular pressure. (PMID:19445930)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioptger4bENSDARG00000035415
danio_rerioptger4aENSDARG00000059236
mus_musculusPtger4ENSMUSG00000039942
rattus_norvegicusPtger4ENSRNOG00000013240

Paralogs (7): TBXA2R (ENSG00000006638), PTGER3 (ENSG00000050628), PTGFR (ENSG00000122420), PTGER2 (ENSG00000125384), PTGIR (ENSG00000160013), PTGER1 (ENSG00000160951), PTGDR (ENSG00000168229)

Protein

Protein identifiers

Prostaglandin E2 receptor EP4 subtypeP35408 (reviewed: P35408)

Alternative names: Prostanoid EP4 receptor

All UniProt accessions (1): P35408

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.

Subunit / interactions. Interacts with FEM1A.

Subcellular location. Cell membrane.

Tissue specificity. High in intestine and in peripheral blood mononuclear cells; low in lung, kidney, thymus, uterus, vasculature and brain. Not found in liver, heart, retina oe skeletal muscle.

Post-translational modifications. Phosphorylation mediates agonist-mediated desensitization by promoting cytoplasmic retention.

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

RefSeq proteins (1): NP_000949* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR001244Prostglndn_DP_rcptFamily
IPR001758Prost_EP4_rcptFamily
IPR008365Prostanoid_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (50 total): helix 12, topological domain 8, transmembrane region 7, turn 7, modified residue 4, strand 4, region of interest 2, compositionally biased region 2, chain 1, glycosylation site 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDBMethodResolution (Å)
9JQZELECTRON MICROSCOPY2.65
9JQYELECTRON MICROSCOPY2.92
8GCPELECTRON MICROSCOPY3.1
8GDBELECTRON MICROSCOPY3.1
5YWYX-RAY DIFFRACTION3.2
8GD9ELECTRON MICROSCOPY3.2
7D7MELECTRON MICROSCOPY3.3
8GDAELECTRON MICROSCOPY3.3
8GCMELECTRON MICROSCOPY3.5
5YHLX-RAY DIFFRACTION4.2

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P35408-F171.510.38

Antibody-complex structures (SAbDab): 85YHL, 5YWY, 7D7M, 8GCM, 8GCP, 8GD9, 8GDA, 8GDB

Functional residue map

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

Post-translational modifications (4): 374, 377, 379, 382

Disulfide bonds (1): 92–170

Glycosylation sites (1): 7

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-391908Prostanoid ligand receptors
R-HSA-418555G alpha (s) signalling events

MSigDB gene sets: 509 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BENPORATH_ES_WITH_H3K27ME3, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_INFLAMMATORY_RESPONSE, REACTOME_EICOSANOID_LIGAND_BINDING_RECEPTORS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION

GO Biological Process (25): negative regulation of cytokine production (GO:0001818), positive regulation of cytokine production (GO:0001819), inflammatory response (GO:0006954), immune response (GO:0006955), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), positive regulation of cytosolic calcium ion concentration (GO:0007204), JNK cascade (GO:0007254), response to mechanical stimulus (GO:0009612), negative regulation of integrin activation (GO:0033624), response to prostaglandin E (GO:0034695), T-helper cell differentiation (GO:0042093), negative regulation of inflammatory response (GO:0050728), positive regulation of inflammatory response (GO:0050729), regulation of stress fiber assembly (GO:0051492), bone development (GO:0060348), ERK1 and ERK2 cascade (GO:0070371), cellular response to mechanical stimulus (GO:0071260), cellular response to prostaglandin E stimulus (GO:0071380), negative regulation of eosinophil extravasation (GO:2000420), MAPK cascade (GO:0000165), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), response to lipid (GO:0033993)

GO Molecular Function (4): prostaglandin E receptor activity (GO:0004957), G protein-coupled receptor activity (GO:0004930), prostaglandin receptor activity (GO:0004955), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Eicosanoid ligand-binding receptors1
GPCR downstream signalling1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cytokine production2
regulation of cytokine production2
G protein-coupled receptor signaling pathway2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway2
MAPK cascade2
inflammatory response2
regulation of inflammatory response2
negative regulation of gene expression1
negative regulation of multicellular organismal process1
positive regulation of gene expression1
positive regulation of multicellular organismal process1
defense response1
immune system process1
response to stimulus1
adenylate cyclase activity1
adenylate cyclase activator activity1
adenylate cyclase inhibitor activity1
regulation of biological quality1
response to external stimulus1
response to abiotic stimulus1
negative regulation of protein-containing complex assembly1
integrin activation1
regulation of integrin activation1
response to prostaglandin1
response to alcohol1
response to ketone1
CD4-positive, alpha-beta T cell differentiation1
negative regulation of defense response1
negative regulation of response to external stimulus1
positive regulation of defense response1
positive regulation of response to external stimulus1
regulation of actin filament bundle assembly1
stress fiber assembly1
regulation of actomyosin structure organization1
skeletal system development1
animal organ development1
response to mechanical stimulus1
cellular response to abiotic stimulus1
cellular response to external stimulus1
response to prostaglandin E1

Protein interactions and networks

STRING

2446 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PTGER4PTGER1P34995976
PTGER4PTGS2P35354884
PTGER4PTGESO14684872
PTGER4ARRB1P49407816
PTGER4PRKACAP17612787
PTGER4PRKACGP22612787
PTGER4PRKACBP22694786
PTGER4PTGS1P23219739
PTGER4PTGES2Q9H7Z7672
PTGER4PTGER3P43115667
PTGER4FEM1AQ9BSK4639
PTGER4HAS2Q92819631
PTGER4LTC4SQ16873625
PTGER4HPGDP15428625
PTGER4CALB2P22676621

IntAct

44 interactions, top by confidence:

ABTypeScore
ARRB1SRCpsi-mi:“MI:0914”(association)0.620
SRCPTGER4psi-mi:“MI:0915”(physical association)0.400
ACTN4PTGER4psi-mi:“MI:0915”(physical association)0.370
CRADDPTGER4psi-mi:“MI:0915”(physical association)0.370
CFAP298PTGER4psi-mi:“MI:0915”(physical association)0.370
HOPXPTGER4psi-mi:“MI:0915”(physical association)0.370
NUP153PTGER4psi-mi:“MI:0915”(physical association)0.370
PRDX1PTGER4psi-mi:“MI:0915”(physical association)0.370
PSMC1PTGER4psi-mi:“MI:0915”(physical association)0.370
PPP1R3FPTGER4psi-mi:“MI:0915”(physical association)0.370
CDPF1PTGER4psi-mi:“MI:0915”(physical association)0.370
SLC39A8PTGER4psi-mi:“MI:0915”(physical association)0.370
SND1PTGER4psi-mi:“MI:0915”(physical association)0.370
SLBPPTGER4psi-mi:“MI:0915”(physical association)0.370
ST13PTGER4psi-mi:“MI:0915”(physical association)0.370
WDR19PTGER4psi-mi:“MI:0915”(physical association)0.370
ANAPC7PTGER4psi-mi:“MI:0915”(physical association)0.370
ACY3PTGER4psi-mi:“MI:0915”(physical association)0.370
ATXN10PTGER4psi-mi:“MI:0915”(physical association)0.370
BNIP1PTGER4psi-mi:“MI:0915”(physical association)0.370
BIN1PTGER4psi-mi:“MI:0915”(physical association)0.370
CTNND2PTGER4psi-mi:“MI:0915”(physical association)0.370
RNF220PTGER4psi-mi:“MI:0915”(physical association)0.370
RTF2PTGER4psi-mi:“MI:0915”(physical association)0.370
CRY2PTGER4psi-mi:“MI:0915”(physical association)0.370
DPF1PTGER4psi-mi:“MI:0915”(physical association)0.370
DSTPTGER4psi-mi:“MI:0915”(physical association)0.370
EHMT2PTGER4psi-mi:“MI:0915”(physical association)0.370
GJC2PTGER4psi-mi:“MI:0915”(physical association)0.370
HMOX1PTGER4psi-mi:“MI:0915”(physical association)0.370

BioGRID (49): PSEN1 (Affinity Capture-Western), PTGER4 (Affinity Capture-Western), PTGER4 (Affinity Capture-Western), PTGER4 (Affinity Capture-RNA), ACTN4 (Two-hybrid), CRADD (Two-hybrid), C21orf59 (Two-hybrid), HOPX (Two-hybrid), NUP153 (Two-hybrid), PRDX1 (Two-hybrid), PSMC1 (Two-hybrid), PPP1R3F (Two-hybrid), CDPF1 (Two-hybrid), SLC39A8 (Two-hybrid), SND1 (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: A0A4W3GG95, A0A6I8PUB9, A5PLE7, A7YY44, B0UXR0, B5X337, D4A7K7, E7FEL0, E9QJ73, O00254, O42179, O88634, P25116, P26824, P30558, P30937, P31391, P32240, P32246, P32249, P32250, P35366, P35383, P35408, P41231, P41232, P43114, P43657, P49660, P51436, P51676, P56482, P58826, P97266, Q09QM4, Q13304, Q149R9, Q1RMI1, Q28691, Q2KTE1

SIGNOR signaling

5 interactions.

AEffectBMechanism
“prostaglandin E2”up-regulatesPTGER4“chemical activation”
PTGER4“up-regulates activity”GNASbinding
PTGER4“up-regulates activity”GNALbinding
PTGER4“up-regulates activity”GNAI1binding
“prostaglandin E2(1-)”“up-regulates activity”PTGER4“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance69
Likely benign2
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

605 predictions. Top by Δscore:

VariantEffectΔscore
5:40681858:GTG:Gdonor_gain1.0000
5:40681861:G:GGdonor_gain1.0000
5:40681832:T:TAdonor_gain0.9900
5:40681833:G:GAdonor_gain0.9900
5:40681861:GTG:Gdonor_loss0.9900
5:40681862:T:TGdonor_loss0.9900
5:40681863:G:GTdonor_loss0.9900
5:40691774:TGCAG:Tacceptor_loss0.9900
5:40691775:GCAG:Gacceptor_loss0.9900
5:40691776:CAG:Cacceptor_loss0.9900
5:40685533:GC:Gdonor_gain0.9800
5:40691778:GGTGC:Gacceptor_gain0.9800
5:40680225:GCGA:Gdonor_gain0.9700
5:40681857:CGTG:Cdonor_gain0.9700
5:40681858:GTGG:Gdonor_gain0.9700
5:40681859:TG:Tdonor_gain0.9700
5:40681859:TGGT:Tdonor_gain0.9700
5:40681860:GG:Gdonor_gain0.9700
5:40681860:GGTG:Gdonor_gain0.9700
5:40681864:AGTGA:Adonor_loss0.9700
5:40691777:A:AGacceptor_gain0.9700
5:40691778:G:GGacceptor_gain0.9700
5:40680229:G:GGdonor_gain0.9600
5:40681856:TCGTG:Tdonor_gain0.9600
5:40691778:GGT:Gacceptor_gain0.9600
5:40691774:T:TAacceptor_gain0.9500
5:40685534:C:Gdonor_gain0.9400
5:40691770:C:Gacceptor_gain0.9300
5:40679965:G:GTdonor_gain0.9100
5:40680949:A:AGacceptor_gain0.9100

AlphaMissense

3141 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:40681098:C:AN35K1.000
5:40681098:C:GN35K1.000
5:40681190:T:CL66P1.000
5:40681210:A:CS73R1.000
5:40681212:C:AS73R1.000
5:40681212:C:GS73R1.000
5:40691890:T:AW327R1.000
5:40691890:T:CW327R1.000
5:40681084:G:AG31R0.999
5:40681084:G:CG31R0.999
5:40681084:G:TG31W0.999
5:40681085:G:AG31E0.999
5:40681093:G:CG34R0.999
5:40681094:G:AG34D0.999
5:40681106:C:AA38D0.999
5:40681153:T:CF54L0.999
5:40681155:C:AF54L0.999
5:40681155:C:GF54L0.999
5:40681175:T:CL61P0.999
5:40681178:C:AA62D0.999
5:40681187:A:CD65A0.999
5:40681187:A:GD65G0.999
5:40681187:A:TD65V0.999
5:40681188:C:AD65E0.999
5:40681188:C:GD65E0.999
5:40681195:G:CG68R0.999
5:40681333:A:CS114R0.999
5:40681335:T:AS114R0.999
5:40681335:T:GS114R0.999
5:40681343:G:CR117P0.999

dbSNP variants (sampled 300 via entrez): RS1000074054 (5:40695014 A>G), RS1000102264 (5:40679929 G>A,C), RS1000106105 (5:40742199 T>G), RS1000154750 (5:40741137 T>A), RS1000176147 (5:40694561 T>G), RS1000178110 (5:40713726 A>T), RS1000207940 (5:40738801 G>A), RS1000240468 (5:40739092 T>C), RS1000242889 (5:40717498 A>G), RS1000294253 (5:40700951 A>C), RS1000373435 (5:40707227 C>T), RS1000423515 (5:40741390 C>T), RS1000547078 (5:40737141 C>CA), RS1000548016 (5:40692801 T>C,G), RS1000578047 (5:40737453 A>G)

Disease associations

OMIM: gene MIM:601586 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

StudyTraitp-value
GCST000066_1Crohn’s disease4.000000e-07
GCST000207_29Crohn’s disease7.000000e-27
GCST000424_12Multiple sclerosis2.000000e-07
GCST000879_53Crohn’s disease7.000000e-36
GCST000964_16Ulcerative colitis3.000000e-09
GCST001149_6Ankylosing spondylitis3.000000e-07
GCST001198_70Multiple sclerosis3.000000e-16
GCST001300_2Gastric cancer8.000000e-29
GCST001438_4Crohn’s disease2.000000e-11
GCST001505_1Multiple sclerosis1.000000e-09
GCST001652_7Crohn’s disease1.000000e-06
GCST001725_81Inflammatory bowel disease2.000000e-82
GCST002083_17Self-reported allergy8.000000e-11
GCST002992_8Gastric cancer5.000000e-06
GCST003097_11Pediatric autoimmune diseases8.000000e-11
GCST003814_7Selective IgA deficiency5.000000e-07
GCST004290_4Multiple sclerosis2.000000e-06
GCST005038_17Allergic disease (asthma, hay fever or eczema)6.000000e-10
GCST005529_19Ankylosing spondylitis5.000000e-06
GCST005529_37Ankylosing spondylitis4.000000e-06
GCST007536_4Serum urea levels6.000000e-10
GCST007856_11Colorectal cancer or advanced adenoma4.000000e-09
GCST007856_23Colorectal cancer or advanced adenoma4.000000e-21
GCST008062_2Blood urea nitrogen levels4.000000e-84
GCST008730_1Crohn’s disease3.000000e-06
GCST90002403_398Red blood cell count6.000000e-09
GCST90011899_183Aspartate aminotransferase levels1.000000e-29
GCST90013445_25Type 1 diabetes2.000000e-14
GCST90013445_39Type 1 diabetes2.000000e-14

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0004305erythrocyte count
EFO:0004736aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1836 (SINGLE PROTEIN), CHEMBL2363068 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 19,549 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL548DINOPROSTONE414,939
CHEMBL815DINOPROST43,118
CHEMBL3301604RALINEPAG3260
CHEMBL1628698BGC-20-1531 FREE BASE267
CHEMBL3039498GRAPIPRANT2983
CHEMBL3260771BGC-20-1531219
CHEMBL3670685PALUPIPRANT253
CHEMBL3707245OMIDENEPAG281
CHEMBL5314911BMS-986310229

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs4133101Toxicity3celecoxibColorectal Neoplasms

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs4133101PTGER432.501celecoxib
rs10512734PTGER40.000
rs11749180PTGER4, TTC330.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Prostanoid receptors

Most potent curated ligand interactions (52 total), top 25:

LigandActionAffinityParameter
L902688Agonist10.3pEC50
[3H]PGE2Full agonist9.52pKd
KMN-159Agonist9.42pKi
11-deoxy-PGE1Agonist9.33pEC50
ER819762Antagonist9.25pKi
MK-2894Antagonist9.25pKi
rivenprostFull agonist9.2pKi
MF 498Antagonist9.15pKi
ONO-AE1-437Agonist9.15pKi
11-deoxy-PGE2Full agonist9.0pKi
CP734432Agonist9.0pEC50
TCS 2510Agonist8.92pKi
ONO-AE3-208Antagonist8.9pKi
PGE1Full agonist8.8pKi
PGD2Full agonist8.77pEC50
evatanepagAntagonist8.6pKi
ONO-AE2-227Antagonist8.57pKi
CJ-042794Antagonist8.51pKi
13,14-dihydro-PGE1Full agonist8.5pKi
L-161,982 (EP4A)Agonist8.5pKi
compound 47 [PMID: 35640059]Antagonist8.3pIC50
palupiprantAntagonist8.2pKi
MB-28767Full agonist8.0pKi
BGC201531Antagonist7.9pKi
grapiprantAntagonist7.89pKi

Binding affinities (BindingDB)

340 measured of 403 human assays (405 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
7-[(5R)-3,3-difluoro-5-[(E,3S)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acidEC500.01 nMUS-9180116: Difluorolactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions
7-[(5R)-3,3-difluoro-5-[(E,3S,4S)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acidEC500.059 nMUS-9180116: Difluorolactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions
5-[3-[(5R)-3,3-difluoro-5-[(E,3S,4S)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acidEC500.15 nMUS-9180116: Difluorolactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions
4-[2-[1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2,3-dihydroindol-7-yl]ethyl]benzoic acidKI0.3 nMUS-9546162: Compounds and methods for skin repair
NSC_5311503KI0.3 nM
NSC_3080928KI0.4 nM
4-[(1S)-1-[[2,5-dibromo-4-[(3-chlorophenyl)methyl]thiophene-3-carbonyl]amino]ethyl]benzoic acidKI0.47 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-{1-[({2,5-Dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}-carbonyl)amino]cyclopropyl}benzoic AcidKI0.5 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
2,5-dimethyl-N-[1-[4-(2H-tetrazol-5-yl)phenyl]cyclopropyl]-4-[[4-(trifluoromethyl)phenyl]methyl]thiophene-3-carboxamideKI0.6 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
2,5-dimethyl-N-[1-[4-(2H-tetrazol-5-yl)phenyl]cyclopropyl]-4-[[3-(trifluoromethyl)phenyl]methyl]thiophene-3-carboxamideKI0.7 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[(1S)-1-[[5-bromo-4-[(3-chlorophenyl)methyl]thiophene-3-carbonyl]amino]ethyl]benzoic acidKI0.71 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[(1S)-1-[[2,5-dichloro-4-[[3-(trifluoromethyl)phenyl]methyl]thiophene-3-carbonyl]amino]ethyl]benzoic acidKI0.8 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-{1-[({2,5-Dimethyl-4-[3-(trifluoromethyl)benzyl]-3-thienyl}-carbonyl)amino]cyclopropyl}benzoic AcidKI0.8 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
2-[3-[[5-(3-fluorophenyl)-2-methoxy-3-methylphenyl]methylamino]-2,4-dimethylphenoxy]acetic acidEC500.9 nMUS-9249085: Aniline derivatives, their preparation and their therapeutic application
4-[(1R)-1-({[2,5-Dichloro-4-(3-chlorobenzyl)-3-thienyl]carbonyl}amino)ethyl]benzoic acidKI0.9 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[({[2,5-Dichloro-4-(3-chlorobenzyl)-3-thienyl]carbonyl}amino)methyl]benzoic acidKI0.9 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[4-Cyano-2-({[(1R,2R)-6′-(methylcarbamoyl)-2′,3′-dihydrospiro[cyclopropane-1, 1′-inden]-2-yl]carbonyl}amino)phenyl]butanoic acidIC501.2 nMUS-10077247: Tricyclic spiro compound
4-{4-Cyano-2-[({2′R, 4S)-6-[(1-methyl 1H-pyrazol-4-yl)carbamoyl]-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl}carbonyl)amino]phenyl}butanoic acidIC501.3 nMUS-10077247: Tricyclic spiro compound
4-[(1S)-1-({[2,5-Dichloro-4-(3-chlorobenzyl)-3-thienyl]carbonyl}-amino)ethyl]benzoic AcidKI1.3 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-{(1S)-1-[({2,5-Dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}-carbonyl)amino]ethyl}benzoic acidKI1.4 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[4-cyano-2-[[(1’R,4S)-7-fluoro-6-(2-methoxyethylcarbamoyl)spiro[2,3-dihydrochromene-4,2’-cyclopropane]-1’-carbonyl]amino]phenyl]butanoic acidIC501.6 nMUS-10077247: Tricyclic spiro compound
CAS_41598-07-6KI1.7 nM
4-[(1S)-1-[[2,5-dichloro-4-[(3-chlorophenyl)-hydroxymethyl]thiophene-3-carbonyl]amino]ethyl]benzoic acidKI1.8 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
2-[4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)-3-methylphenyl]methylamino]-2-methylphenoxy]acetic acidEC502 nMUS-9249085: Aniline derivatives, their preparation and their therapeutic application
2-[3-[[5-(3-fluorophenyl)-2,3-dimethylphenyl]methylamino]-2,4-dimethylphenoxy]acetic acidEC502 nMUS-9249085: Aniline derivatives, their preparation and their therapeutic application
4-[2-[1-[(3-fluorophenyl)methyl]-2,3-dihydroindol-7-yl]ethyl]benzoic acidKI2 nMUS-9546162: Compounds and methods for skin repair
4-[4-Cyano-2-({[(2′R,4S)-6-(1H-pyrazol-1-yl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC502.4 nMUS-10077247: Tricyclic spiro compound
4-{(1S)-1-[({2,5-Dimethyl-4-[3-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]ethyl}benzoic AcidKI2.4 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[4-cyano-2-[[(1’R,4S)-6-(methylcarbamoyl)spiro[2,3-dihydrochromene-4,2’-cyclopropane]-1’-carbonyl]amino]phenyl]butanoic acidIC502.5 nMUS-10077247: Tricyclic spiro compound
4-[4-Cyano-2-({[(2′R,4S)-6-(3-pyridazinylcarbamoyl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC502.5 nMUS-10077247: Tricyclic spiro compound
4-[4-Cyano-2-({[(2′R,4S)-6-(propylcarbamoyl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC502.5 nMUS-10077247: Tricyclic spiro compound
5-chloro-3-[(3-chlorophenyl)methyl]-N-[1-[4-(2H-tetrazol-5-yl)phenyl]ethyl]thiophene-2-carboxamideKI2.6 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[4-Cyano-2-({[(2′R,4S)-6-(5-methyl-1,3,4-oxadiazol-2-yl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC502.7 nMUS-10077247: Tricyclic spiro compound
4-{4-Cyano-2-[({(1R,2R)-6′-[(1-methyl-1H-pyrazol-4-yl)carbamoyl]-2′,3′-dihydrospiro[cyclopropane-1,1′-inden]-2-yl}carbonyl)amino]phenyl}butanoic acidIC502.7 nMUS-10077247: Tricyclic spiro compound
4-[4-cyano-2-[[(1’R,4S)-6-(3-methyl-1,2,4-oxadiazol-5-yl)spiro[2,3-dihydrochromene-4,2’-cyclopropane]-1’-carbonyl]amino]phenyl]butanoic acidIC502.8 nMUS-10077247: Tricyclic spiro compound
2-[2,4-difluoro-3-[[3-fluoro-5-(3-fluorophenyl)-2-methylphenyl]methylamino]phenoxy]acetic acidEC503 nMUS-9249085: Aniline derivatives, their preparation and their therapeutic application
2-[3-[[3-fluoro-5-(3-fluorophenyl)-2-methylphenyl]methylamino]-2,4-dimethylphenoxy]acetic acidEC503 nMUS-9249085: Aniline derivatives, their preparation and their therapeutic application
4-[4-Cyano-2-({[(2′R,4S)-6-(ethylcarbamoyl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC503 nMUS-10077247: Tricyclic spiro compound
4-{4-Cyano-2-[({(1R,2R)-6′-[(2-methoxyethyl)carbamoyl]-2′,3′-dihydrospiro[cyclopropane-1,1′-inden]-2-yl}carbonyl)amino]phenyl}butanoic acidIC503 nMUS-10077247: Tricyclic spiro compound
4-[(1S)-1-({[4-(3-Chlorobenzyl)-2,5-dimethyl-3-thienyl]carbonyl}-amino)ethyl]benzoic AcidKI3.1 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[4-cyano-2-[[(1’R,4S)-6-[[(2S)-1-methoxypropan-2-yl]carbamoyl]spiro[2,3-dihydrochromene-4,2’-cyclopropane]-1’-carbonyl]amino]phenyl]butanoic acidIC503.3 nMUS-10077247: Tricyclic spiro compound
4-[4-Cyano-2-({[(2′R,4S)-6-(1,2-oxazol-3-ylcarbamoyl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC503.4 nMUS-10077247: Tricyclic spiro compound
4-[2-[[(1’R,4S)-6-[(1-tert-butylpyrazol-4-yl)carbamoyl]spiro[2,3-dihydrochromene-4,2’-cyclopropane]-1’-carbonyl]amino]-4-cyanophenyl]butanoic acidIC503.4 nMUS-10077247: Tricyclic spiro compound
4-[4-Cyano-2-({[(2′R,4S)-6-(1,2-oxazol-5-ylcarbamoyl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC503.4 nMUS-10077247: Tricyclic spiro compound
4-[(1S)-1-({[4-(4-Chlorobenzyl)-2,5-dimethyl-3-thienyl]carbonyl}-amino)ethyl]benzoicAcidKI3.4 nMUS-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands
4-[2-[[(1’R,4S)-6-(tert-butylcarbamoyl)spiro[2,3-dihydrochromene-4,2’-cyclopropane]-1’-carbonyl]amino]-4-cyanophenyl]butanoic acidIC503.5 nMUS-10077247: Tricyclic spiro compound
4-[4-Cyano-2-({[(2′R,4S)-6-(6-methoxy-3-pyridinyl)-2,3-dihydrospiro[chromene-4, 1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC503.5 nMUS-10077247: Tricyclic spiro compound
4-[4-Cyano-2-({[(2′R,4S)-6-(1-methyl-1H-1,2,3-triazol-4-yl)-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl]carbonyl}amino)phenyl]butanoic acidIC503.5 nMUS-10077247: Tricyclic spiro compound
4-{4-Cyano-2-[({(2′R,4S)-6-[(1-methyl-1H-pyrazol-5-yl)carbamoyl]-2, 3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl}carbonyl)amino]phenyl}butanoic acidIC503.6 nMUS-10077247: Tricyclic spiro compound
4-{4-Cyano-2-[({(2′R,4S)-6-[(2,2-difluoroethyl)carbamoyl]-2,3-dihydrospiro[chromene-4,1′-cyclopropan]-2′-yl}carbonyl)amino]phenyl}butanoic acidIC503.7 nMUS-10077247: Tricyclic spiro compound

ChEMBL bioactivities

1744 potent at pChembl≥5 of 1778 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00EC500.01nMCHEMBL3975743
11.00EC500.01nMCHEMBL3959605
11.00EC500.01nMCHEMBL292964
10.85EC500.014nMCHEMBL5945805
10.79EC500.0162nMCHEMBL3937596
10.72EC500.019nMCHEMBL5838727
10.70EC500.02nMDINOPROSTONE
10.70Ki0.02nMCHEMBL258332
10.70EC500.02nMCHEMBL222715
10.70EC500.02nMCHEMBL5436415
10.68EC500.021nMCHEMBL3955128
10.64EC500.023nMCHEMBL3897335
10.52EC500.03nMCHEMBL258332
10.52EC500.03nMCHEMBL272276
10.46EC500.035nMCHEMBL3895047
10.42EC500.038nMCHEMBL3902065
10.42EC500.038nMCHEMBL3918816
10.40EC500.04nMCHEMBL3974652
10.40EC500.04nMCHEMBL222677
10.40EC500.04nMCHEMBL251294
10.33EC500.047nMCHEMBL3895047
10.30EC500.05nMCHEMBL64804
10.30EC500.05nMCHEMBL3906016
10.30Ki0.05nMCHEMBL272276
10.30EC500.05nMCHEMBL5395111
10.23EC500.059nMCHEMBL3893847
10.23EC500.059nMCHEMBL3982139
10.23EC500.059nMCHEMBL3955128
10.20EC500.063nMCHEMBL3916499
10.19EC500.065nMCHEMBL42027
10.12EC500.075nMCHEMBL3923027
10.10EC500.079nMCHEMBL3916499
10.09Ki0.082nMCHEMBL3923027
10.06EC500.088nMCHEMBL3918816
10.00EC500.1nMCHEMBL3960625
10.00Ki0.1nMCHEMBL3916499
10.00EC500.1nMCHEMBL251505
10.00EC500.1nMCHEMBL249953
9.96EC500.11nMCHEMBL3949856
9.96Ki0.11nMDINOPROSTONE
9.96Ki0.11nMCHEMBL1669013
9.92Ki0.12nMCHEMBL3895047
9.92Ki0.12nMCHEMBL256873
9.85Ki0.14nMCHEMBL64804
9.85EC500.142nMCHEMBL292964
9.85Ki0.14nMDINOPROSTONE
9.82EC500.15nMCHEMBL3982139
9.82EC500.15nMCHEMBL3891907
9.80Ki0.16nMCHEMBL1669017
9.80Ki0.16nMCHEMBL1669012

PubChem BioAssay actives

1129 with measured affinity, of 1722 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.

CompoundAssayTypeValueUnit
7-[(2R)-2-[(E,3S)-3-hydroxy-4-phenylbut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid1970857: Agonist activity at EP4 (unknown origin) assessed as increase in calcium fluxec50<0.0001uM
4-[2-[(2R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid320754: Agonist activity at human EP4 receptor by cAMP assayec50<0.0001uM
4-[2-[(2S)-2-[(3R)-3-[3-(4-chloro-2-methylphenyl)phenyl]-3-hydroxypropyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid281511: Functional activity at human EP4 receptorec50<0.0001uM
4-[2-[(2R)-2-[(E,3S)-3-hydroxyhept-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid308197: Agonist activity at EP4 receptor expressed in HEK293 cells assessed as cAMP accumulationec50<0.0001uM
4-[2-[(2R)-2-[(E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid320753: Displacement of [3H]PGE4 from human EP4 receptorki<0.0001uM
dinoprostone1587874: Agonist activity at human EP4 receptor expressed in HEK293T/17 cells assessed as increase in GalphaS-mediated CREB activation measured after 6 to 24 hrs by SEAP reporter gene-based chemiluminescence assayec50<0.0001uM
7-[(5R)-3,3-difluoro-5-[(E,3S)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid1587874: Agonist activity at human EP4 receptor expressed in HEK293T/17 cells assessed as increase in GalphaS-mediated CREB activation measured after 6 to 24 hrs by SEAP reporter gene-based chemiluminescence assayec50<0.0001uM
4-[2-[(2R)-2-[(E,3S)-3-hydroxy-4-phenylbut-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid320754: Agonist activity at human EP4 receptor by cAMP assayec50<0.0001uM
4-[2-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl]-5-oxocyclopentyl]ethylsulfanyl]butanoic acid1587874: Agonist activity at human EP4 receptor expressed in HEK293T/17 cells assessed as increase in GalphaS-mediated CREB activation measured after 6 to 24 hrs by SEAP reporter gene-based chemiluminescence assayec50<0.0001uM
N-benzylsulfonyl-7-[(2R)-2-[(E,3S)-3-hydroxy-4-phenylbut-1-enyl]-5-oxopyrrolidin-1-yl]heptanamide1970857: Agonist activity at EP4 (unknown origin) assessed as increase in calcium fluxec500.0001uM
7-[(2R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid1587874: Agonist activity at human EP4 receptor expressed in HEK293T/17 cells assessed as increase in GalphaS-mediated CREB activation measured after 6 to 24 hrs by SEAP reporter gene-based chemiluminescence assayec500.0001uM
4-[2-[(2R)-2-[(1E,3Z)-4-methylocta-1,3-dienyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid308197: Agonist activity at EP4 receptor expressed in HEK293 cells assessed as cAMP accumulationec500.0001uM
4-[2-[2-[(3S)-4-(3-bromophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid310293: Agonist activity at human prostaglandin EP4 receptorec500.0001uM
2-(2-acetyl-6-methoxyphenyl)-N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0001uM
1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(4-methylphenyl)sulfonylurea568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0001uM
7-[(5R)-3,3-difluoro-5-[(E,3S,4S)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid1587874: Agonist activity at human EP4 receptor expressed in HEK293T/17 cells assessed as increase in GalphaS-mediated CREB activation measured after 6 to 24 hrs by SEAP reporter gene-based chemiluminescence assayec500.0001uM
4-[2-[2-[4-(3-chlorophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid310293: Agonist activity at human prostaglandin EP4 receptorec500.0002uM
4-[2-[2-[4-(3-bromophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid310293: Agonist activity at human prostaglandin EP4 receptorec500.0002uM
4-[2-[(2R)-2-[(E,3S)-5-cyclobutyl-3-hydroxypent-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid281511: Functional activity at human EP4 receptorec500.0002uM
N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]-2-[2-(trifluoromethoxy)phenyl]acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0002uM
4-[(1S)-1-[[1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid549652: Agonist activity at human prostanoid EP4 receptor expressed in HEK293 cells assessed as potentiation of PGE2-induced cAMP accumulation by scintillation proximity assayec500.0002uM
4-[1-[[1-[[4-(trifluoromethyl)phenyl]methyl]indole-7-carbonyl]amino]cyclopropyl]benzoic acid484030: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation countingki0.0002uM
1-(2-chlorophenyl)sulfonyl-3-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]urea568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0002uM
1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(2-methylphenyl)sulfonylurea568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0002uM
1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(2-methoxyphenyl)sulfonylurea568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0002uM
3-[4-[2-[[2-(2-methoxyphenyl)acetyl]amino]ethyl]phenyl]-N,N,5,7-tetramethyl-1-benzothiophene-2-carboxamide552143: Binding affinity to EP4 receptorki0.0002uM
N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-2-(2-methoxyphenyl)acetamide568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0002uM
3-[2-[[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]amino]-2-oxoethyl]-4-methoxybenzoic acid568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0002uM
N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-2-(3-methoxy-2-pyridinyl)acetamide568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0002uM
N-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)phenyl]methylsulfonyl]-2-phenylacetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0003uM
2-(2,6-dichlorophenyl)-N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0003uM
N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]-2-(2-ethoxyphenyl)acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0003uM
N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]-2-[2-(difluoromethoxy)phenyl]acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0003uM
2-(2-chlorophenyl)-N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0003uM
4-[[4-[4-(difluoromethoxy)phenyl]anilino]methyl]-5-methyl-N-(2-methylphenyl)sulfonylfuran-2-carboxamide1139728: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in cell membranes by scintillation countingki0.0003uM
4-[(1S)-1-[[1-[(3,5-dibromophenyl)methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid549650: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation countingki0.0003uM
4-[(1S)-1-[[1-[(3,4-dichlorophenyl)methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid549650: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation countingki0.0003uM
4-[1-[[5-chloro-1-[[4-(trifluoromethyl)phenyl]methyl]indole-7-carbonyl]amino]cyclopropyl]benzoic acid484030: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation countingki0.0003uM
1-(2,6-dichlorophenyl)sulfonyl-3-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]urea568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0003uM
1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(2,6-dimethoxyphenyl)sulfonylurea568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0003uM
N-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methylsulfonyl]-2-phenylacetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0003uM
4-[2-[(2R)-2-[(E,3S)-3-(1-butylcyclobutyl)-3-hydroxyprop-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid320754: Agonist activity at human EP4 receptor by cAMP assayec500.0003uM
4-[(1S)-1-[[1-[(4-phenylphenyl)methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid549650: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation countingki0.0003uM
2-(2-chlorophenyl)-N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]acetamide568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0003uM
3-[4-[[1-(2-methoxyphenyl)cyclopropanecarbonyl]sulfamoylmethyl]phenyl]-N,N,5,7-tetramethyl-1-benzothiophene-2-carboxamide552143: Binding affinity to EP4 receptorki0.0003uM
2-(2,4-dichlorophenyl)-N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]acetamide568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0003uM
N-[2-[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]ethyl]-2-(2-methoxyphenyl)acetamide568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assayki0.0003uM
4-[[5-[3-(hydroxymethyl)phenyl]-2-methylbenzoyl]amino]-3,5-dimethylbenzoic acid1272648: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as inhibition of PGE2-stimulated cAMP production after 1 hr by HTRF assayic500.0003uM
N-benzylsulfonyl-3-[[(1S)-2-(4,5-diphenyl-1,3-oxazol-2-yl)cyclohex-2-en-1-yl]methyl]benzamide238968: Inhibition of [3H]PGE-2 binding to human prostanoid EP4 receptorki0.0003uM
N-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)phenyl]methylsulfonyl]-2-(2,5-dimethoxyphenyl)acetamide316652: Binding affinity to human EP4 receptor expressed in HEK293 cellski0.0004uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Estradiolaffects cotreatment, increases expression, decreases expression, decreases reaction6
Valproic Acidaffects cotreatment, increases expression, decreases expression6
sodium arsenitedecreases expression, affects cotreatment, increases abundance, increases expression, increases stability4
Benzo(a)pyreneincreases expression, decreases expression3
nickel sulfateincreases response to substance, increases secretion, increases chemical synthesis, increases reaction, increases expression (+1 more)2
mercuric bromideaffects cotreatment, increases expression2
AH 23848affects binding, affects cotreatment, decreases reaction, decreases activity2
Vehicle Emissionsaffects cotreatment, decreases expression, increases expression2
Cisplatindecreases expression, increases expression2
Lipopolysaccharidesdecreases reaction, increases expression, affects response to substance, affects cotreatment2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Tobacco Smoke Pollutiondecreases expression, increases expression2
Dinoprostoneincreases reaction, decreases reaction, increases expression, increases activity, increases chemical synthesis (+2 more)2
Particulate Matterdecreases expression, increases abundance2
aristolochic acid Iincreases expression1
bisphenol Adecreases expression1
diethyl phthalateaffects cotreatment, decreases expression, decreases reaction1
2-methyl-4-isothiazolin-3-oneincreases expression1
diisononyl phthalateaffects cotreatment, decreases expression, decreases reaction1
trichostatin Aincreases expression1
2-butenaldecreases expression1
3,4-dichloroanilinedecreases expression1
afimoxifeneincreases expression, affects reaction1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
cobaltous chloridedecreases expression1
butyraldehydeincreases expression1
3,4,5,3’,4’-pentachlorobiphenylincreases expression1
manganese chlorideaffects cotreatment, decreases expression, increases abundance1
ochratoxin Aincreases expression1
diisobutyl phthalateaffects cotreatment, decreases expression, decreases reaction1

ChEMBL screening assays

288 unique, capped per target: 207 binding, 80 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1009665BindingInhibition of EP4 receptorDiscovery 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
CHEMBL1047106FunctionalInhibition of EP4 expressed in HEK293 cells assessed as inhibition of PGE2-induced cAMP productionDiscovery and optimization of CRTH2 and DP dual antagonists. — Bioorg Med Chem Lett
CHEMBL4326154ADMETDisplacement of [3H]prostaglandin E2 from recombinant human full length EP4 receptor expressed in Chem-1 cell membranes after 60 mins by liquid scintillation countingIdentification of a Selective, Non-Prostanoid EP2 Receptor Agonist for the Treatment of Glaucoma: Omidenepag and its Prodrug Omidenepag Isopropyl. — J Med Chem

Cellosaurus cell lines

11 cell lines: 7 cancer cell line, 4 transformed cell line

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

CellosaurusNameCategorySex
CVCL_B7YYAbcam Raji PTGER4 KOCancer cell lineMale
CVCL_B9ZPAbcam THP-1 PTGER4 KOCancer cell lineMale
CVCL_C0TMACTOne PTGER4Transformed cell lineFemale
CVCL_C7BDAbcam PC-3 PTGER4 KOCancer cell lineMale
CVCL_E2I6HAP1 PTGER4 (-) 1Cancer cell lineMale
CVCL_E2I7HAP1 PTGER4 (-) 2Cancer cell lineMale
CVCL_H367293 c18/EP4Transformed cell lineFemale
CVCL_KZ63PathHunter HEK 293 PTGER4 beta-arrestinTransformed cell lineFemale
CVCL_LB19PathHunter U2OS PTGER4 Activated GPCR InternalizationCancer cell lineFemale
CVCL_LB20PathHunter U2OS PTGER4 beta-arrestinCancer cell lineFemale

Clinical trials (associated diseases)

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