Target Information

Target General Infomation
Target ID
T18876
Former ID
TTDC00151
Target Name
Prostaglandin E2 receptor, EP4 subtype
Gene Name
PTGER4
Synonyms
EP sub 4 receptor; PGE receptor, EP4 subtype; Prostanoid EP4 receptor; PTGER4
Target Type
Clinical Trial
Disease Acute heart failure [ICD9: 428; ICD10: I50]
Asthma [ICD10: J45]
Fracture [ICD10: M48.5]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Migraine [ICD9: 346; ICD10: G43]
Osteoarthritis; Pain [ICD9: 338, 715,780; ICD10: M15-M19, M47, R52, G89]
Osteoarthritis [ICD9: 715; ICD10: M15-M19, M47]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Ulcerative colitis [ICD9: 556; ICD10: K51]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T18876
UniProt ID
P35408
Sequence
MSTPGVNSSASLSPDRLNSPVTIPAVMFIFGVVGNLVAIVVLCKSRKEQKETTFYTLVCG
LAVTDLLGTLLVSPVTIATYMKGQWPGGQPLCEYSTFILLFFSLSGLSIICAMSVERYLA
INHAYFYSHYVDKRLAGLTLFAVYASNVLFCALPNMGLGSSRLQYPDTWCFIDWTTNVTA
HAAYSYMYAGFSSFLILATVLCNVLVCGALLRMHRQFMRRTSLGTEQHHAAAAASVASRG
HPAASPALPRLSDFRRRRSFRRIAGAEIQMVILLIATSLVVLICSIPLVVRVFVNQLYQP
SLEREVSKNPDLQAIRIASVNPILDPWIYILLRKTVLSKAIEKIKCLFCRIGGSRRERSG
QHCSDSQRTSSAMSGHSRSFISRELKEISSTSQTLLPDLSLPDLSENGLGGRNLLPGVPG
MGLAQEDTTSLRTLRISETSDSSQGQDSESVLLVDEAGGSGRAGPAPKGSSLQVTFPSET
LNLSEKCI
Drugs and Mode of Action
Drug(s) BGC-20-1531 Drug Info Phase 2 Migraine [522648], [540329]
ONO-AE1-437 Drug Info Phase 2 Asthma [543189]
RQ-00000007 (oral) Drug Info Phase 2 Pain [541167], [548890]
EP4-R antagonist Drug Info Phase 1 Osteoarthritis; Pain [549532]
ONO-4232 Drug Info Phase 1 Acute heart failure [549519]
PGF2alpha Drug Info Clinical trial Solid tumours [532003]
ONO-4819 Drug Info Discontinued in Phase 2 Fracture [539230], [547505]
Agonist 1-OH-PGE1 Drug Info [534478]
11-deoxy-PGE1 Drug Info [525852]
11-deoxy-PGE2 Drug Info [534595]
13,14-dihydro-PGE1 Drug Info [525852]
16,16-dimethyl-PGE2 Drug Info [534478]
19(R)-OH-PGE2 Drug Info [534595]
butaprost (free acid form) Drug Info [534595]
carbacyclin Drug Info [534478]
cicaprost Drug Info [525673]
CP734432 Drug Info [530142]
KAG-308 Drug Info [543780]
L902688 Drug Info [543780]
M&B 28767 Drug Info [534478]
ONO-4232 Drug Info [549789]
ONO-4819 Drug Info [536219], [536465], [537179]
ONO-AE1-329 Drug Info [525735]
ONO-AE1-437 Drug Info [527162]
PF-04475270 Drug Info [543780]
PGD2 Drug Info [534595]
PGF2alpha Drug Info [534595]
TCS 2510 Drug Info [543780]
U46619 Drug Info [534595]
Inhibitor 3-(2-((E)-3-phenylprop-1-enyl)phenyl)acrylic acid Drug Info [528393]
3-(2-(4-methoxycinnamyl)phenyl)acrylic acid Drug Info [528393]
3-(2-(naphthalen-2-ylmethyl)phenyl)acrylic acid Drug Info [528393]
3-(2-cinnamylphenyl)acrylic acid Drug Info [528393]
8-aza-11-deoxyprostaglandin E1 Drug Info [527306]
FR-181157 Drug Info [527530]
Antagonist AH23848 Drug Info [534595]
BGC-20-1531 Drug Info [544082]
CR-5790 Drug Info [543780]
EP4-R antagonist Drug Info [543780]
ER819762 Drug Info [530872]
GW 627368 Drug Info [527379]
MK-2894 Drug Info [543780]
ONO-AE2-227 Drug Info [526239]
ONO-AE3-208 Drug Info [526303]
ONO-AE3-240 Drug Info [526517]
RQ-00000007 (oral) Drug Info [550316]
RQ-00000008 Drug Info [543780]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Inflammatory mediator regulation of TRP channels
Renin secretion
Pathways in cancer
NetPath Pathway FSH Signaling Pathway
IL2 Signaling Pathway
IL4 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
Reactome Prostanoid ligand receptors
G alpha (s) signalling events
WikiPathways Prostaglandin Synthesis and Regulation
GPCRs, Class A Rhodopsin-like
Vitamin D Receptor Pathway
Small Ligand GPCRs
GPCR ligand binding
GPCR downstream signaling
References
Ref 522648ClinicalTrials.gov (NCT00888680) Double-blind, Placebo-controlled Study of BGC20-1531 in Migraine. U.S. National Institutes of Health.
Ref 532003Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.
Ref 539230(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1930).
Ref 540329(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3380).
Ref 541167(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5858).
Ref 543189(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8541).
Ref 547505Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016907)
Ref 548890Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029996)
Ref 549519Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039411)
Ref 549532Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039864)
Ref 525673The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta. 2000 Jan 17;1483(2):285-93.
Ref 525735The role of prostaglandin E receptor subtypes (EP1, EP2, EP3, and EP4) in bone resorption: an analysis using specific agonists for the respective EPs. Endocrinology. 2000 Apr;141(4):1554-9.
Ref 525852Pharmacological characterization of [(3)H]-prostaglandin E(2) binding to the cloned human EP(4) prostanoid receptor. Br J Pharmacol. 2000 Aug;130(8):1919-26.
Ref 526239Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis. Cancer Res. 2002 Jan 1;62(1):28-32.
Ref 526303The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J Clin Invest. 2002 Apr;109(7):883-93.
Ref 526517Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. J Exp Med. 2003 Jan 20;197(2):221-32.
Ref 527162An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo. Pediatr Res. 2004 Oct;56(4):586-90. Epub 2004 Aug 4.
Ref 527306J Med Chem. 2004 Dec 2;47(25):6124-7.Lactams as EP4 prostanoid receptor agonists. 3. Discovery of N-ethylbenzoic acid 2-pyrrolidinones as subtype selective agents.
Ref 527379Piglet saphenous vein contains multiple relaxatory prostanoid receptors: evidence for EP4, EP2, DP and IP receptor subtypes. Br J Pharmacol. 2005 Feb;144(3):405-15.
Ref 527530J Med Chem. 2005 May 5;48(9):3103-6.Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective human prostaglandin EP(4) receptor antagonists.
Ref 528393Bioorg Med Chem Lett. 2006 Nov 1;16(21):5639-42. Epub 2006 Aug 22.Comparison between two classes of selective EP(3) antagonists and their biological activities.
Ref 530142Ocular pharmacokinetics and hypotensive activity of PF-04475270, an EP4 prostaglandin agonist in preclinical models. Exp Eye Res. 2009 Nov;89(5):608-17.
Ref 530872A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310.
Ref 534478Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24.
Ref 534595Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41.
Ref 536219Effects on improvement of blood flow in the chronically compressed cauda equina: comparison between a selective prostaglandin E receptor (EP4) agonist and a prostaglandin E1 derivate. Spine (Phila Pa1976). 2006 Apr 15;31(8):869-72.
Ref 536465Prostaglandin E2 EP4 agonist (ONO-4819) accelerates BMP-induced osteoblastic differentiation. Bone. 2007 Oct;41(4):543-8. Epub 2007 Jun 29.
Ref 537179Effect of a prostaglandin EP4 receptor agonist on early fixation of hydroxyapatite/titanium composite- and titanium-coated rough-surfaced implants in ovariectomized rats. J Biomed Mater Res A. 2009 Mar 25.
Ref 543780(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 343).
Ref 544082BGC20-1531, a novel, potent and selective prostanoid EP4 receptor antagonist: a putative new treatment for migraine headache. Br J Pharmacol. 2009 January; 156(2): 316-327.
Ref 549789ONO-4232, an EP4-selective Agonist, Improves Left Ventricular Diastolic Dysfunction and Ameliorates Acute and Chronic Heart Failure in Animal Models. Circulation. 2012; 126: A15345.
Ref 550316Clinical pipeline report, company report or official report of Avarx.

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