PTGER4
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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
| Field | Value |
|---|---|
| HGNC ID | HGNC:9596 |
| Approved symbol | PTGER4 |
| Name | prostaglandin E receptor 4 |
| Location | 5p13.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | EP4 |
| Ensembl gene | ENSG00000171522 |
| Ensembl biotype | protein_coding |
| OMIM | 601586 |
| Entrez | 5734 |
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
| Exon | Start | End |
|---|---|---|
| ENSE00001143202 | 40691779 | 40693735 |
| ENSE00001143213 | 40680951 | 40681860 |
| ENSE00002024751 | 40679915 | 40680478 |
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 ID | TPM avg | Samples expressed |
|---|---|---|
| 56230 | 22.9924 | 1361 |
| 56232 | 0.9865 | 120 |
| 56227 | 0.8471 | 332 |
| 56233 | 0.6239 | 219 |
| 56228 | 0.2674 | 117 |
| 56229 | 0.2565 | 106 |
| 56231 | 0.1783 | 57 |
| 203535 | 0.0270 | 11 |
Top tissues by expression
295 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| palpebral conjunctiva | UBERON:0001812 | 98.94 | gold quality |
| jejunal mucosa | UBERON:0000399 | 98.00 | gold quality |
| renal glomerulus | UBERON:0000074 | 97.72 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 97.46 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 97.31 | gold quality |
| bronchial epithelial cell | CL:0002328 | 96.91 | gold quality |
| colonic mucosa | UBERON:0000317 | 96.73 | gold quality |
| visceral pleura | UBERON:0002401 | 95.71 | gold quality |
| synovial joint | UBERON:0002217 | 95.65 | gold quality |
| pleura | UBERON:0000977 | 95.55 | gold quality |
| germinal epithelium of ovary | UBERON:0001304 | 95.38 | gold quality |
| epithelium of bronchus | UBERON:0002031 | 95.31 | gold quality |
| parietal pleura | UBERON:0002400 | 95.31 | gold quality |
| bronchus | UBERON:0002185 | 95.14 | gold quality |
| superficial temporal artery | UBERON:0001614 | 94.87 | gold quality |
| jejunum | UBERON:0002115 | 94.04 | gold quality |
| lower lobe of lung | UBERON:0008949 | 93.81 | gold quality |
| mammary duct | UBERON:0001765 | 93.49 | gold quality |
| mucosa of urinary bladder | UBERON:0001259 | 93.47 | gold quality |
| vena cava | UBERON:0004087 | 93.31 | gold quality |
| duodenum | UBERON:0002114 | 93.30 | gold quality |
| skin of hip | UBERON:0001554 | 93.05 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 93.03 | gold quality |
| epithelium of mammary gland | UBERON:0003244 | 92.66 | gold quality |
| granulocyte | CL:0000094 | 92.34 | gold quality |
| mucosa of paranasal sinus | UBERON:0005030 | 91.93 | gold quality |
| leukocyte | CL:0000738 | 91.44 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 91.40 | gold quality |
| mononuclear cell | CL:0000842 | 91.23 | gold quality |
| bone marrow | UBERON:0002371 | 91.11 | gold quality |
Single-cell (SCXA)
Detected in 6 experiment(s), a significant marker in 4.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-CURD-46 | yes | 45.44 |
| E-CURD-88 | yes | 39.78 |
| E-CURD-122 | yes | 36.58 |
| E-CURD-77 | no | 608.36 |
| E-MTAB-5061 | no | 4.29 |
| E-ANND-3 | no | 0.00 |
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):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-4795-3P | 100.00 | 74.62 | 4024 |
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-4510 | 100.00 | 66.60 | 2050 |
| HSA-MIR-6127 | 100.00 | 66.76 | 2188 |
| HSA-MIR-6129 | 100.00 | 66.46 | 2080 |
| HSA-MIR-6130 | 100.00 | 66.69 | 2012 |
| HSA-MIR-6133 | 100.00 | 66.48 | 2064 |
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-513B-5P | 99.99 | 69.96 | 2150 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-32-5P | 99.98 | 75.21 | 1964 |
| HSA-MIR-92A-3P | 99.98 | 75.21 | 1960 |
| HSA-MIR-92B-3P | 99.98 | 75.25 | 1955 |
| HSA-MIR-25-3P | 99.98 | 74.60 | 1817 |
| HSA-MIR-363-3P | 99.98 | 74.72 | 1821 |
| HSA-MIR-367-3P | 99.98 | 74.83 | 1819 |
| HSA-MIR-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-27A-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-27B-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-9985 | 99.98 | 72.11 | 2939 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-1229-3P | 99.97 | 66.49 | 906 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
| HSA-MIR-548AA | 99.96 | 70.64 | 3753 |
| HSA-MIR-548AP-3P | 99.96 | 70.64 | 3753 |
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
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | ptger4b | ENSDARG00000035415 |
| danio_rerio | ptger4a | ENSDARG00000059236 |
| mus_musculus | Ptger4 | ENSMUSG00000039942 |
| rattus_norvegicus | Ptger4 | ENSRNOG00000013240 |
Paralogs (7): TBXA2R (ENSG00000006638), PTGER3 (ENSG00000050628), PTGFR (ENSG00000122420), PTGER2 (ENSG00000125384), PTGIR (ENSG00000160013), PTGER1 (ENSG00000160951), PTGDR (ENSG00000168229)
Protein
Protein identifiers
Prostaglandin E2 receptor EP4 subtype — P35408 (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)
| ID | Name | Type |
|---|---|---|
| IPR000276 | GPCR_Rhodpsn | Family |
| IPR001244 | Prostglndn_DP_rcpt | Family |
| IPR001758 | Prost_EP4_rcpt | Family |
| IPR008365 | Prostanoid_rcpt | Family |
| IPR017452 | GPCR_Rhodpsn_7TM | Domain |
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.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 9JQZ | ELECTRON MICROSCOPY | 2.65 |
| 9JQY | ELECTRON MICROSCOPY | 2.92 |
| 8GCP | ELECTRON MICROSCOPY | 3.1 |
| 8GDB | ELECTRON MICROSCOPY | 3.1 |
| 5YWY | X-RAY DIFFRACTION | 3.2 |
| 8GD9 | ELECTRON MICROSCOPY | 3.2 |
| 7D7M | ELECTRON MICROSCOPY | 3.3 |
| 8GDA | ELECTRON MICROSCOPY | 3.3 |
| 8GCM | ELECTRON MICROSCOPY | 3.5 |
| 5YHL | X-RAY DIFFRACTION | 4.2 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P35408-F1 | 71.51 | 0.38 |
Antibody-complex structures (SAbDab): 8 — 5YHL, 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
| ID | Pathway |
|---|---|
| R-HSA-391908 | Prostanoid ligand receptors |
| R-HSA-418555 | G 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:
| Category | Pathways |
|---|---|
| Eicosanoid ligand-binding receptors | 1 |
| GPCR downstream signalling | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cytokine production | 2 |
| regulation of cytokine production | 2 |
| G protein-coupled receptor signaling pathway | 2 |
| adenylate cyclase-modulating G protein-coupled receptor signaling pathway | 2 |
| MAPK cascade | 2 |
| inflammatory response | 2 |
| regulation of inflammatory response | 2 |
| negative regulation of gene expression | 1 |
| negative regulation of multicellular organismal process | 1 |
| positive regulation of gene expression | 1 |
| positive regulation of multicellular organismal process | 1 |
| defense response | 1 |
| immune system process | 1 |
| response to stimulus | 1 |
| adenylate cyclase activity | 1 |
| adenylate cyclase activator activity | 1 |
| adenylate cyclase inhibitor activity | 1 |
| regulation of biological quality | 1 |
| response to external stimulus | 1 |
| response to abiotic stimulus | 1 |
| negative regulation of protein-containing complex assembly | 1 |
| integrin activation | 1 |
| regulation of integrin activation | 1 |
| response to prostaglandin | 1 |
| response to alcohol | 1 |
| response to ketone | 1 |
| CD4-positive, alpha-beta T cell differentiation | 1 |
| negative regulation of defense response | 1 |
| negative regulation of response to external stimulus | 1 |
| positive regulation of defense response | 1 |
| positive regulation of response to external stimulus | 1 |
| regulation of actin filament bundle assembly | 1 |
| stress fiber assembly | 1 |
| regulation of actomyosin structure organization | 1 |
| skeletal system development | 1 |
| animal organ development | 1 |
| response to mechanical stimulus | 1 |
| cellular response to abiotic stimulus | 1 |
| cellular response to external stimulus | 1 |
| response to prostaglandin E | 1 |
Protein interactions and networks
STRING
2446 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| PTGER4 | PTGER1 | P34995 | 976 |
| PTGER4 | PTGS2 | P35354 | 884 |
| PTGER4 | PTGES | O14684 | 872 |
| PTGER4 | ARRB1 | P49407 | 816 |
| PTGER4 | PRKACA | P17612 | 787 |
| PTGER4 | PRKACG | P22612 | 787 |
| PTGER4 | PRKACB | P22694 | 786 |
| PTGER4 | PTGS1 | P23219 | 739 |
| PTGER4 | PTGES2 | Q9H7Z7 | 672 |
| PTGER4 | PTGER3 | P43115 | 667 |
| PTGER4 | FEM1A | Q9BSK4 | 639 |
| PTGER4 | HAS2 | Q92819 | 631 |
| PTGER4 | LTC4S | Q16873 | 625 |
| PTGER4 | HPGD | P15428 | 625 |
| PTGER4 | CALB2 | P22676 | 621 |
IntAct
44 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| ARRB1 | SRC | psi-mi:“MI:0914”(association) | 0.620 |
| SRC | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.400 |
| ACTN4 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| CRADD | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| CFAP298 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| HOPX | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| NUP153 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| PRDX1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| PSMC1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| PPP1R3F | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| CDPF1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| SLC39A8 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| SND1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| SLBP | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ST13 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| WDR19 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ANAPC7 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ACY3 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ATXN10 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| BNIP1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| BIN1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| CTNND2 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| RNF220 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| RTF2 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| CRY2 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| DPF1 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| DST | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| EHMT2 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| GJC2 | PTGER4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| HMOX1 | PTGER4 | psi-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.
| A | Effect | B | Mechanism |
|---|---|---|---|
| “prostaglandin E2” | up-regulates | PTGER4 | “chemical activation” |
| PTGER4 | “up-regulates activity” | GNAS | binding |
| PTGER4 | “up-regulates activity” | GNAL | binding |
| PTGER4 | “up-regulates activity” | GNAI1 | binding |
| “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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 69 |
| Likely benign | 2 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
605 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 5:40681858:GTG:G | donor_gain | 1.0000 |
| 5:40681861:G:GG | donor_gain | 1.0000 |
| 5:40681832:T:TA | donor_gain | 0.9900 |
| 5:40681833:G:GA | donor_gain | 0.9900 |
| 5:40681861:GTG:G | donor_loss | 0.9900 |
| 5:40681862:T:TG | donor_loss | 0.9900 |
| 5:40681863:G:GT | donor_loss | 0.9900 |
| 5:40691774:TGCAG:T | acceptor_loss | 0.9900 |
| 5:40691775:GCAG:G | acceptor_loss | 0.9900 |
| 5:40691776:CAG:C | acceptor_loss | 0.9900 |
| 5:40685533:GC:G | donor_gain | 0.9800 |
| 5:40691778:GGTGC:G | acceptor_gain | 0.9800 |
| 5:40680225:GCGA:G | donor_gain | 0.9700 |
| 5:40681857:CGTG:C | donor_gain | 0.9700 |
| 5:40681858:GTGG:G | donor_gain | 0.9700 |
| 5:40681859:TG:T | donor_gain | 0.9700 |
| 5:40681859:TGGT:T | donor_gain | 0.9700 |
| 5:40681860:GG:G | donor_gain | 0.9700 |
| 5:40681860:GGTG:G | donor_gain | 0.9700 |
| 5:40681864:AGTGA:A | donor_loss | 0.9700 |
| 5:40691777:A:AG | acceptor_gain | 0.9700 |
| 5:40691778:G:GG | acceptor_gain | 0.9700 |
| 5:40680229:G:GG | donor_gain | 0.9600 |
| 5:40681856:TCGTG:T | donor_gain | 0.9600 |
| 5:40691778:GGT:G | acceptor_gain | 0.9600 |
| 5:40691774:T:TA | acceptor_gain | 0.9500 |
| 5:40685534:C:G | donor_gain | 0.9400 |
| 5:40691770:C:G | acceptor_gain | 0.9300 |
| 5:40679965:G:GT | donor_gain | 0.9100 |
| 5:40680949:A:AG | acceptor_gain | 0.9100 |
AlphaMissense
3141 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 5:40681098:C:A | N35K | 1.000 |
| 5:40681098:C:G | N35K | 1.000 |
| 5:40681190:T:C | L66P | 1.000 |
| 5:40681210:A:C | S73R | 1.000 |
| 5:40681212:C:A | S73R | 1.000 |
| 5:40681212:C:G | S73R | 1.000 |
| 5:40691890:T:A | W327R | 1.000 |
| 5:40691890:T:C | W327R | 1.000 |
| 5:40681084:G:A | G31R | 0.999 |
| 5:40681084:G:C | G31R | 0.999 |
| 5:40681084:G:T | G31W | 0.999 |
| 5:40681085:G:A | G31E | 0.999 |
| 5:40681093:G:C | G34R | 0.999 |
| 5:40681094:G:A | G34D | 0.999 |
| 5:40681106:C:A | A38D | 0.999 |
| 5:40681153:T:C | F54L | 0.999 |
| 5:40681155:C:A | F54L | 0.999 |
| 5:40681155:C:G | F54L | 0.999 |
| 5:40681175:T:C | L61P | 0.999 |
| 5:40681178:C:A | A62D | 0.999 |
| 5:40681187:A:C | D65A | 0.999 |
| 5:40681187:A:G | D65G | 0.999 |
| 5:40681187:A:T | D65V | 0.999 |
| 5:40681188:C:A | D65E | 0.999 |
| 5:40681188:C:G | D65E | 0.999 |
| 5:40681195:G:C | G68R | 0.999 |
| 5:40681333:A:C | S114R | 0.999 |
| 5:40681335:T:A | S114R | 0.999 |
| 5:40681335:T:G | S114R | 0.999 |
| 5:40681343:G:C | R117P | 0.999 |
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):
| Study | Trait | p-value |
|---|---|---|
| GCST000066_1 | Crohn’s disease | 4.000000e-07 |
| GCST000207_29 | Crohn’s disease | 7.000000e-27 |
| GCST000424_12 | Multiple sclerosis | 2.000000e-07 |
| GCST000879_53 | Crohn’s disease | 7.000000e-36 |
| GCST000964_16 | Ulcerative colitis | 3.000000e-09 |
| GCST001149_6 | Ankylosing spondylitis | 3.000000e-07 |
| GCST001198_70 | Multiple sclerosis | 3.000000e-16 |
| GCST001300_2 | Gastric cancer | 8.000000e-29 |
| GCST001438_4 | Crohn’s disease | 2.000000e-11 |
| GCST001505_1 | Multiple sclerosis | 1.000000e-09 |
| GCST001652_7 | Crohn’s disease | 1.000000e-06 |
| GCST001725_81 | Inflammatory bowel disease | 2.000000e-82 |
| GCST002083_17 | Self-reported allergy | 8.000000e-11 |
| GCST002992_8 | Gastric cancer | 5.000000e-06 |
| GCST003097_11 | Pediatric autoimmune diseases | 8.000000e-11 |
| GCST003814_7 | Selective IgA deficiency | 5.000000e-07 |
| GCST004290_4 | Multiple sclerosis | 2.000000e-06 |
| GCST005038_17 | Allergic disease (asthma, hay fever or eczema) | 6.000000e-10 |
| GCST005529_19 | Ankylosing spondylitis | 5.000000e-06 |
| GCST005529_37 | Ankylosing spondylitis | 4.000000e-06 |
| GCST007536_4 | Serum urea levels | 6.000000e-10 |
| GCST007856_11 | Colorectal cancer or advanced adenoma | 4.000000e-09 |
| GCST007856_23 | Colorectal cancer or advanced adenoma | 4.000000e-21 |
| GCST008062_2 | Blood urea nitrogen levels | 4.000000e-84 |
| GCST008730_1 | Crohn’s disease | 3.000000e-06 |
| GCST90002403_398 | Red blood cell count | 6.000000e-09 |
| GCST90011899_183 | Aspartate aminotransferase levels | 1.000000e-29 |
| GCST90013445_25 | Type 1 diabetes | 2.000000e-14 |
| GCST90013445_39 | Type 1 diabetes | 2.000000e-14 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004305 | erythrocyte count |
| EFO:0004736 | aspartate 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).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL548 | DINOPROSTONE | 4 | 14,939 |
| CHEMBL815 | DINOPROST | 4 | 3,118 |
| CHEMBL3301604 | RALINEPAG | 3 | 260 |
| CHEMBL1628698 | BGC-20-1531 FREE BASE | 2 | 67 |
| CHEMBL3039498 | GRAPIPRANT | 2 | 983 |
| CHEMBL3260771 | BGC-20-1531 | 2 | 19 |
| CHEMBL3670685 | PALUPIPRANT | 2 | 53 |
| CHEMBL3707245 | OMIDENEPAG | 2 | 81 |
| CHEMBL5314911 | BMS-986310 | 2 | 29 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB clinical annotations
1 annotations.
| Variant | Type | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs4133101 | Toxicity | 3 | celecoxib | Colorectal Neoplasms |
PharmGKB variants
3 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs4133101 | PTGER4 | 3 | 2.50 | 1 | celecoxib |
| rs10512734 | PTGER4 | 0.00 | 0 | ||
| rs11749180 | PTGER4, TTC33 | 0.00 | 0 |
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:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| L902688 | Agonist | 10.3 | pEC50 |
| [3H]PGE2 | Full agonist | 9.52 | pKd |
| KMN-159 | Agonist | 9.42 | pKi |
| 11-deoxy-PGE1 | Agonist | 9.33 | pEC50 |
| ER819762 | Antagonist | 9.25 | pKi |
| MK-2894 | Antagonist | 9.25 | pKi |
| rivenprost | Full agonist | 9.2 | pKi |
| MF 498 | Antagonist | 9.15 | pKi |
| ONO-AE1-437 | Agonist | 9.15 | pKi |
| 11-deoxy-PGE2 | Full agonist | 9.0 | pKi |
| CP734432 | Agonist | 9.0 | pEC50 |
| TCS 2510 | Agonist | 8.92 | pKi |
| ONO-AE3-208 | Antagonist | 8.9 | pKi |
| PGE1 | Full agonist | 8.8 | pKi |
| PGD2 | Full agonist | 8.77 | pEC50 |
| evatanepag | Antagonist | 8.6 | pKi |
| ONO-AE2-227 | Antagonist | 8.57 | pKi |
| CJ-042794 | Antagonist | 8.51 | pKi |
| 13,14-dihydro-PGE1 | Full agonist | 8.5 | pKi |
| L-161,982 (EP4A) | Agonist | 8.5 | pKi |
| compound 47 [PMID: 35640059] | Antagonist | 8.3 | pIC50 |
| palupiprant | Antagonist | 8.2 | pKi |
| MB-28767 | Full agonist | 8.0 | pKi |
| BGC201531 | Antagonist | 7.9 | pKi |
| grapiprant | Antagonist | 7.89 | pKi |
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.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 7-[(5R)-3,3-difluoro-5-[(E,3S)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid | EC50 | 0.01 nM | US-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 acid | EC50 | 0.059 nM | US-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 acid | EC50 | 0.15 nM | US-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 acid | KI | 0.3 nM | US-9546162: Compounds and methods for skin repair |
| NSC_5311503 | KI | 0.3 nM | |
| NSC_3080928 | KI | 0.4 nM | |
| 4-[(1S)-1-[[2,5-dibromo-4-[(3-chlorophenyl)methyl]thiophene-3-carbonyl]amino]ethyl]benzoic acid | KI | 0.47 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 4-{1-[({2,5-Dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}-carbonyl)amino]cyclopropyl}benzoic Acid | KI | 0.5 nM | US-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-carboxamide | KI | 0.6 nM | US-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-carboxamide | KI | 0.7 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 4-[(1S)-1-[[5-bromo-4-[(3-chlorophenyl)methyl]thiophene-3-carbonyl]amino]ethyl]benzoic acid | KI | 0.71 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 4-[(1S)-1-[[2,5-dichloro-4-[[3-(trifluoromethyl)phenyl]methyl]thiophene-3-carbonyl]amino]ethyl]benzoic acid | KI | 0.8 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 4-{1-[({2,5-Dimethyl-4-[3-(trifluoromethyl)benzyl]-3-thienyl}-carbonyl)amino]cyclopropyl}benzoic Acid | KI | 0.8 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 2-[3-[[5-(3-fluorophenyl)-2-methoxy-3-methylphenyl]methylamino]-2,4-dimethylphenoxy]acetic acid | EC50 | 0.9 nM | US-9249085: Aniline derivatives, their preparation and their therapeutic application |
| 4-[(1R)-1-({[2,5-Dichloro-4-(3-chlorobenzyl)-3-thienyl]carbonyl}amino)ethyl]benzoic acid | KI | 0.9 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 4-[({[2,5-Dichloro-4-(3-chlorobenzyl)-3-thienyl]carbonyl}amino)methyl]benzoic acid | KI | 0.9 nM | US-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 acid | IC50 | 1.2 nM | US-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 acid | IC50 | 1.3 nM | US-10077247: Tricyclic spiro compound |
| 4-[(1S)-1-({[2,5-Dichloro-4-(3-chlorobenzyl)-3-thienyl]carbonyl}-amino)ethyl]benzoic Acid | KI | 1.3 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 4-{(1S)-1-[({2,5-Dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}-carbonyl)amino]ethyl}benzoic acid | KI | 1.4 nM | US-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 acid | IC50 | 1.6 nM | US-10077247: Tricyclic spiro compound |
| CAS_41598-07-6 | KI | 1.7 nM | |
| 4-[(1S)-1-[[2,5-dichloro-4-[(3-chlorophenyl)-hydroxymethyl]thiophene-3-carbonyl]amino]ethyl]benzoic acid | KI | 1.8 nM | US-8969394: Thiophenecarboxamide derivatives as EP4 receptor ligands |
| 2-[4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)-3-methylphenyl]methylamino]-2-methylphenoxy]acetic acid | EC50 | 2 nM | US-9249085: Aniline derivatives, their preparation and their therapeutic application |
| 2-[3-[[5-(3-fluorophenyl)-2,3-dimethylphenyl]methylamino]-2,4-dimethylphenoxy]acetic acid | EC50 | 2 nM | US-9249085: Aniline derivatives, their preparation and their therapeutic application |
| 4-[2-[1-[(3-fluorophenyl)methyl]-2,3-dihydroindol-7-yl]ethyl]benzoic acid | KI | 2 nM | US-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 acid | IC50 | 2.4 nM | US-10077247: Tricyclic spiro compound |
| 4-{(1S)-1-[({2,5-Dimethyl-4-[3-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]ethyl}benzoic Acid | KI | 2.4 nM | US-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 acid | IC50 | 2.5 nM | US-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 acid | IC50 | 2.5 nM | US-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 acid | IC50 | 2.5 nM | US-10077247: Tricyclic spiro compound |
| 5-chloro-3-[(3-chlorophenyl)methyl]-N-[1-[4-(2H-tetrazol-5-yl)phenyl]ethyl]thiophene-2-carboxamide | KI | 2.6 nM | US-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 acid | IC50 | 2.7 nM | US-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 acid | IC50 | 2.7 nM | US-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 acid | IC50 | 2.8 nM | US-10077247: Tricyclic spiro compound |
| 2-[2,4-difluoro-3-[[3-fluoro-5-(3-fluorophenyl)-2-methylphenyl]methylamino]phenoxy]acetic acid | EC50 | 3 nM | US-9249085: Aniline derivatives, their preparation and their therapeutic application |
| 2-[3-[[3-fluoro-5-(3-fluorophenyl)-2-methylphenyl]methylamino]-2,4-dimethylphenoxy]acetic acid | EC50 | 3 nM | US-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 acid | IC50 | 3 nM | US-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 acid | IC50 | 3 nM | US-10077247: Tricyclic spiro compound |
| 4-[(1S)-1-({[4-(3-Chlorobenzyl)-2,5-dimethyl-3-thienyl]carbonyl}-amino)ethyl]benzoic Acid | KI | 3.1 nM | US-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 acid | IC50 | 3.3 nM | US-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 acid | IC50 | 3.4 nM | US-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 acid | IC50 | 3.4 nM | US-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 acid | IC50 | 3.4 nM | US-10077247: Tricyclic spiro compound |
| 4-[(1S)-1-({[4-(4-Chlorobenzyl)-2,5-dimethyl-3-thienyl]carbonyl}-amino)ethyl]benzoicAcid | KI | 3.4 nM | US-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 acid | IC50 | 3.5 nM | US-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 acid | IC50 | 3.5 nM | US-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 acid | IC50 | 3.5 nM | US-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 acid | IC50 | 3.6 nM | US-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 acid | IC50 | 3.7 nM | US-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).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 11.00 | EC50 | 0.01 | nM | CHEMBL3975743 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL3959605 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL292964 |
| 10.85 | EC50 | 0.014 | nM | CHEMBL5945805 |
| 10.79 | EC50 | 0.0162 | nM | CHEMBL3937596 |
| 10.72 | EC50 | 0.019 | nM | CHEMBL5838727 |
| 10.70 | EC50 | 0.02 | nM | DINOPROSTONE |
| 10.70 | Ki | 0.02 | nM | CHEMBL258332 |
| 10.70 | EC50 | 0.02 | nM | CHEMBL222715 |
| 10.70 | EC50 | 0.02 | nM | CHEMBL5436415 |
| 10.68 | EC50 | 0.021 | nM | CHEMBL3955128 |
| 10.64 | EC50 | 0.023 | nM | CHEMBL3897335 |
| 10.52 | EC50 | 0.03 | nM | CHEMBL258332 |
| 10.52 | EC50 | 0.03 | nM | CHEMBL272276 |
| 10.46 | EC50 | 0.035 | nM | CHEMBL3895047 |
| 10.42 | EC50 | 0.038 | nM | CHEMBL3902065 |
| 10.42 | EC50 | 0.038 | nM | CHEMBL3918816 |
| 10.40 | EC50 | 0.04 | nM | CHEMBL3974652 |
| 10.40 | EC50 | 0.04 | nM | CHEMBL222677 |
| 10.40 | EC50 | 0.04 | nM | CHEMBL251294 |
| 10.33 | EC50 | 0.047 | nM | CHEMBL3895047 |
| 10.30 | EC50 | 0.05 | nM | CHEMBL64804 |
| 10.30 | EC50 | 0.05 | nM | CHEMBL3906016 |
| 10.30 | Ki | 0.05 | nM | CHEMBL272276 |
| 10.30 | EC50 | 0.05 | nM | CHEMBL5395111 |
| 10.23 | EC50 | 0.059 | nM | CHEMBL3893847 |
| 10.23 | EC50 | 0.059 | nM | CHEMBL3982139 |
| 10.23 | EC50 | 0.059 | nM | CHEMBL3955128 |
| 10.20 | EC50 | 0.063 | nM | CHEMBL3916499 |
| 10.19 | EC50 | 0.065 | nM | CHEMBL42027 |
| 10.12 | EC50 | 0.075 | nM | CHEMBL3923027 |
| 10.10 | EC50 | 0.079 | nM | CHEMBL3916499 |
| 10.09 | Ki | 0.082 | nM | CHEMBL3923027 |
| 10.06 | EC50 | 0.088 | nM | CHEMBL3918816 |
| 10.00 | EC50 | 0.1 | nM | CHEMBL3960625 |
| 10.00 | Ki | 0.1 | nM | CHEMBL3916499 |
| 10.00 | EC50 | 0.1 | nM | CHEMBL251505 |
| 10.00 | EC50 | 0.1 | nM | CHEMBL249953 |
| 9.96 | EC50 | 0.11 | nM | CHEMBL3949856 |
| 9.96 | Ki | 0.11 | nM | DINOPROSTONE |
| 9.96 | Ki | 0.11 | nM | CHEMBL1669013 |
| 9.92 | Ki | 0.12 | nM | CHEMBL3895047 |
| 9.92 | Ki | 0.12 | nM | CHEMBL256873 |
| 9.85 | Ki | 0.14 | nM | CHEMBL64804 |
| 9.85 | EC50 | 0.142 | nM | CHEMBL292964 |
| 9.85 | Ki | 0.14 | nM | DINOPROSTONE |
| 9.82 | EC50 | 0.15 | nM | CHEMBL3982139 |
| 9.82 | EC50 | 0.15 | nM | CHEMBL3891907 |
| 9.80 | Ki | 0.16 | nM | CHEMBL1669017 |
| 9.80 | Ki | 0.16 | nM | CHEMBL1669012 |
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.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 7-[(2R)-2-[(E,3S)-3-hydroxy-4-phenylbut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid | 1970857: Agonist activity at EP4 (unknown origin) assessed as increase in calcium flux | ec50 | <0.0001 | uM |
| 4-[2-[(2R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 320754: Agonist activity at human EP4 receptor by cAMP assay | ec50 | <0.0001 | uM |
| 4-[2-[(2S)-2-[(3R)-3-[3-(4-chloro-2-methylphenyl)phenyl]-3-hydroxypropyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 281511: Functional activity at human EP4 receptor | ec50 | <0.0001 | uM |
| 4-[2-[(2R)-2-[(E,3S)-3-hydroxyhept-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 308197: Agonist activity at EP4 receptor expressed in HEK293 cells assessed as cAMP accumulation | ec50 | <0.0001 | uM |
| 4-[2-[(2R)-2-[(E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 320753: Displacement of [3H]PGE4 from human EP4 receptor | ki | <0.0001 | uM |
| dinoprostone | 1587874: 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 assay | ec50 | <0.0001 | uM |
| 7-[(5R)-3,3-difluoro-5-[(E,3S)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid | 1587874: 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 assay | ec50 | <0.0001 | uM |
| 4-[2-[(2R)-2-[(E,3S)-3-hydroxy-4-phenylbut-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 320754: Agonist activity at human EP4 receptor by cAMP assay | ec50 | <0.0001 | uM |
| 4-[2-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl]-5-oxocyclopentyl]ethylsulfanyl]butanoic acid | 1587874: 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 assay | ec50 | <0.0001 | uM |
| N-benzylsulfonyl-7-[(2R)-2-[(E,3S)-3-hydroxy-4-phenylbut-1-enyl]-5-oxopyrrolidin-1-yl]heptanamide | 1970857: Agonist activity at EP4 (unknown origin) assessed as increase in calcium flux | ec50 | 0.0001 | uM |
| 7-[(2R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid | 1587874: 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 assay | ec50 | 0.0001 | uM |
| 4-[2-[(2R)-2-[(1E,3Z)-4-methylocta-1,3-dienyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 308197: Agonist activity at EP4 receptor expressed in HEK293 cells assessed as cAMP accumulation | ec50 | 0.0001 | uM |
| 4-[2-[2-[(3S)-4-(3-bromophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid | 310293: Agonist activity at human prostaglandin EP4 receptor | ec50 | 0.0001 | uM |
| 2-(2-acetyl-6-methoxyphenyl)-N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0001 | uM |
| 1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(4-methylphenyl)sulfonylurea | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0001 | uM |
| 7-[(5R)-3,3-difluoro-5-[(E,3S,4S)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid | 1587874: 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 assay | ec50 | 0.0001 | uM |
| 4-[2-[2-[4-(3-chlorophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid | 310293: Agonist activity at human prostaglandin EP4 receptor | ec50 | 0.0002 | uM |
| 4-[2-[2-[4-(3-bromophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid | 310293: Agonist activity at human prostaglandin EP4 receptor | ec50 | 0.0002 | uM |
| 4-[2-[(2R)-2-[(E,3S)-5-cyclobutyl-3-hydroxypent-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 281511: Functional activity at human EP4 receptor | ec50 | 0.0002 | uM |
| N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]-2-[2-(trifluoromethoxy)phenyl]acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0002 | uM |
| 4-[(1S)-1-[[1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid | 549652: Agonist activity at human prostanoid EP4 receptor expressed in HEK293 cells assessed as potentiation of PGE2-induced cAMP accumulation by scintillation proximity assay | ec50 | 0.0002 | uM |
| 4-[1-[[1-[[4-(trifluoromethyl)phenyl]methyl]indole-7-carbonyl]amino]cyclopropyl]benzoic acid | 484030: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation counting | ki | 0.0002 | uM |
| 1-(2-chlorophenyl)sulfonyl-3-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]urea | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0002 | uM |
| 1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(2-methylphenyl)sulfonylurea | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0002 | uM |
| 1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(2-methoxyphenyl)sulfonylurea | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0002 | uM |
| 3-[4-[2-[[2-(2-methoxyphenyl)acetyl]amino]ethyl]phenyl]-N,N,5,7-tetramethyl-1-benzothiophene-2-carboxamide | 552143: Binding affinity to EP4 receptor | ki | 0.0002 | uM |
| N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-2-(2-methoxyphenyl)acetamide | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0002 | uM |
| 3-[2-[[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]amino]-2-oxoethyl]-4-methoxybenzoic acid | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0002 | uM |
| N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-2-(3-methoxy-2-pyridinyl)acetamide | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0002 | uM |
| N-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)phenyl]methylsulfonyl]-2-phenylacetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0003 | uM |
| 2-(2,6-dichlorophenyl)-N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0003 | uM |
| N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]-2-(2-ethoxyphenyl)acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0003 | uM |
| N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]-2-[2-(difluoromethoxy)phenyl]acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0003 | uM |
| 2-(2-chlorophenyl)-N-[[4-(5,9-diethoxy-6-oxo-8H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylphenyl]methylsulfonyl]acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0003 | uM |
| 4-[[4-[4-(difluoromethoxy)phenyl]anilino]methyl]-5-methyl-N-(2-methylphenyl)sulfonylfuran-2-carboxamide | 1139728: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in cell membranes by scintillation counting | ki | 0.0003 | uM |
| 4-[(1S)-1-[[1-[(3,5-dibromophenyl)methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid | 549650: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation counting | ki | 0.0003 | uM |
| 4-[(1S)-1-[[1-[(3,4-dichlorophenyl)methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid | 549650: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation counting | ki | 0.0003 | uM |
| 4-[1-[[5-chloro-1-[[4-(trifluoromethyl)phenyl]methyl]indole-7-carbonyl]amino]cyclopropyl]benzoic acid | 484030: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation counting | ki | 0.0003 | uM |
| 1-(2,6-dichlorophenyl)sulfonyl-3-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]urea | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0003 | uM |
| 1-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]-3-(2,6-dimethoxyphenyl)sulfonylurea | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0003 | uM |
| N-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methylsulfonyl]-2-phenylacetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0003 | uM |
| 4-[2-[(2R)-2-[(E,3S)-3-(1-butylcyclobutyl)-3-hydroxyprop-1-enyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid | 320754: Agonist activity at human EP4 receptor by cAMP assay | ec50 | 0.0003 | uM |
| 4-[(1S)-1-[[1-[(4-phenylphenyl)methyl]-2,3-dihydroindole-7-carbonyl]amino]ethyl]benzoic acid | 549650: Displacement of [3H]PGE2 from human prostanoid EP4 receptor expressed in HEK293-EBNA cells after 60 mins by scintillation counting | ki | 0.0003 | uM |
| 2-(2-chlorophenyl)-N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]acetamide | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0003 | uM |
| 3-[4-[[1-(2-methoxyphenyl)cyclopropanecarbonyl]sulfamoylmethyl]phenyl]-N,N,5,7-tetramethyl-1-benzothiophene-2-carboxamide | 552143: Binding affinity to EP4 receptor | ki | 0.0003 | uM |
| 2-(2,4-dichlorophenyl)-N-[1-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]methyl]cyclopropyl]acetamide | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0003 | uM |
| N-[2-[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)-3-methylphenyl]ethyl]-2-(2-methoxyphenyl)acetamide | 568519: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as PGE2-induced cAMP accumulation by scintillation proximity assay | ki | 0.0003 | uM |
| 4-[[5-[3-(hydroxymethyl)phenyl]-2-methylbenzoyl]amino]-3,5-dimethylbenzoic acid | 1272648: Antagonist activity at human EP4 receptor expressed in HEK293 cells assessed as inhibition of PGE2-stimulated cAMP production after 1 hr by HTRF assay | ic50 | 0.0003 | uM |
| N-benzylsulfonyl-3-[[(1S)-2-(4,5-diphenyl-1,3-oxazol-2-yl)cyclohex-2-en-1-yl]methyl]benzamide | 238968: Inhibition of [3H]PGE-2 binding to human prostanoid EP4 receptor | ki | 0.0003 | uM |
| N-[[4-(4,9-diethoxy-3-oxo-1H-benzo[f]isoindol-2-yl)phenyl]methylsulfonyl]-2-(2,5-dimethoxyphenyl)acetamide | 316652: Binding affinity to human EP4 receptor expressed in HEK293 cells | ki | 0.0004 | uM |
CTD chemical–gene interactions
90 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Estradiol | affects cotreatment, increases expression, decreases expression, decreases reaction | 6 |
| Valproic Acid | affects cotreatment, increases expression, decreases expression | 6 |
| sodium arsenite | decreases expression, affects cotreatment, increases abundance, increases expression, increases stability | 4 |
| Benzo(a)pyrene | increases expression, decreases expression | 3 |
| nickel sulfate | increases response to substance, increases secretion, increases chemical synthesis, increases reaction, increases expression (+1 more) | 2 |
| mercuric bromide | affects cotreatment, increases expression | 2 |
| AH 23848 | affects binding, affects cotreatment, decreases reaction, decreases activity | 2 |
| Vehicle Emissions | affects cotreatment, decreases expression, increases expression | 2 |
| Cisplatin | decreases expression, increases expression | 2 |
| Lipopolysaccharides | decreases reaction, increases expression, affects response to substance, affects cotreatment | 2 |
| Phenylmercuric Acetate | affects cotreatment, increases expression | 2 |
| Tobacco Smoke Pollution | decreases expression, increases expression | 2 |
| Dinoprostone | increases reaction, decreases reaction, increases expression, increases activity, increases chemical synthesis (+2 more) | 2 |
| Particulate Matter | decreases expression, increases abundance | 2 |
| aristolochic acid I | increases expression | 1 |
| bisphenol A | decreases expression | 1 |
| diethyl phthalate | affects cotreatment, decreases expression, decreases reaction | 1 |
| 2-methyl-4-isothiazolin-3-one | increases expression | 1 |
| diisononyl phthalate | affects cotreatment, decreases expression, decreases reaction | 1 |
| trichostatin A | increases expression | 1 |
| 2-butenal | decreases expression | 1 |
| 3,4-dichloroaniline | decreases expression | 1 |
| afimoxifene | increases expression, affects reaction | 1 |
| tris(1,3-dichloro-2-propyl)phosphate | decreases expression | 1 |
| cobaltous chloride | decreases expression | 1 |
| butyraldehyde | increases expression | 1 |
| 3,4,5,3’,4’-pentachlorobiphenyl | increases expression | 1 |
| manganese chloride | affects cotreatment, decreases expression, increases abundance | 1 |
| ochratoxin A | increases expression | 1 |
| diisobutyl phthalate | affects cotreatment, decreases expression, decreases reaction | 1 |
ChEMBL screening assays
288 unique, capped per target: 207 binding, 80 functional, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1009665 | Binding | Inhibition of EP4 receptor | 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 |
| CHEMBL1047106 | Functional | Inhibition of EP4 expressed in HEK293 cells assessed as inhibition of PGE2-induced cAMP production | Discovery and optimization of CRTH2 and DP dual antagonists. — Bioorg Med Chem Lett |
| CHEMBL4326154 | ADMET | Displacement of [3H]prostaglandin E2 from recombinant human full length EP4 receptor expressed in Chem-1 cell membranes after 60 mins by liquid scintillation counting | Identification 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):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B7YY | Abcam Raji PTGER4 KO | Cancer cell line | Male |
| CVCL_B9ZP | Abcam THP-1 PTGER4 KO | Cancer cell line | Male |
| CVCL_C0TM | ACTOne PTGER4 | Transformed cell line | Female |
| CVCL_C7BD | Abcam PC-3 PTGER4 KO | Cancer cell line | Male |
| CVCL_E2I6 | HAP1 PTGER4 (-) 1 | Cancer cell line | Male |
| CVCL_E2I7 | HAP1 PTGER4 (-) 2 | Cancer cell line | Male |
| CVCL_H367 | 293 c18/EP4 | Transformed cell line | Female |
| CVCL_KZ63 | PathHunter HEK 293 PTGER4 beta-arrestin | Transformed cell line | Female |
| CVCL_LB19 | PathHunter U2OS PTGER4 Activated GPCR Internalization | Cancer cell line | Female |
| CVCL_LB20 | PathHunter U2OS PTGER4 beta-arrestin | Cancer cell line | Female |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Targeted by drugs: Alprostadil, Beraprost, Dinoprost, Dinoprostone, Epoprostenol, Iloprost, Misoprostol, Treprostinil
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): common variable immunodeficiency, gastric carcinoma, selective IgA deficiency disease