Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG1QMU)

• DTT Name: Prostaglandin E2 receptor EP1 (PTGER1)
• Synonyms: Prostanoid EP1 receptor; Prostaglandin E2 receptor EP1 subtype; PGE2 receptor EP1 subtype; PGE receptor, EP1 subtype; PGE receptor EP1 subtype; EP1 receptor
• Gene Name: PTGER1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: PE2R1_HUMAN
• TTD ID: T15497
• Sequence:
  MSPCGPLNLSLAGEATTCAAPWVPNTSAVPPSGASPALPIFSMTLGAVSNLLALALLAQA
  AGRLRRRRSAATFLLFVASLLATDLAGHVIPGALVLRLYTAGRAPAGGACHFLGGCMVFF
  GLCPLLLGCGMAVERCVGVTRPLLHAARVSVARARLALAAVAAVALAVALLPLARVGRYE
  LQYPGTWCFIGLGPPGGWRQALLAGLFASLGLVALLAALVCNTLSGLALLRARWRRRSRR
  PPPASGPDSRRRWGAHGPRSASASSASSIASASTFFGGSRSSGSARRARAHDVEMVGQLV
  GIMVVSCICWSPMLVLVALAVGGWSSTSLQRPLFLAVRLASWNQILDPWVYILLRQAVLR
  QLLRLLPPRAGAKGGPAGLGLTPSAWEASSLRSSRHSGLSHF
• Function: The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues. Receptor for prostaglandin E2 (PGE2).
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Prostanoid ligand receptors (R-HSA-391908)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AS-013	DMD7XWS	Thrombosis	DB61-GB90	Phase 3	[2]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[3]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BUTAPROST	DMVYNJZ	Discovery agent	N.A.	Patented	[1]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ZD6416	DM46JIR	Pain	MG30-MG3Z	Discontinued in Phase 2	[4]
ONO-8130	DMBDCL4	Pollakiuria	MF50.1	Terminated	[5]
ONO-8711	DM2VRK7	Pain	MG30-MG3Z	Terminated	[6]

16 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
17-phenyl-omega-trinor-PGE2	DM9OMI3	Discovery agent	N.A.	Investigative	[3]
AH6809	DMKN3R9	Discovery agent	N.A.	Investigative	[3]
carbacyclin	DMMBQYE	Discovery agent	N.A.	Investigative	[7]
cicaprost	DM7ZJ4H	Discovery agent	N.A.	Investigative	[7]
cloprostenol	DMH01JV	Discovery agent	N.A.	Investigative	[8]
GW848687X	DMXA5M9	Discovery agent	N.A.	Investigative	[9]
M&B 28767	DMJQG82	Discovery agent	N.A.	Investigative	[10]
MF266-1	DMSYQP9	Discovery agent	N.A.	Investigative	[11]
ONO-8713	DMD2G65	Discovery agent	N.A.	Investigative	[12]
ONO-DI-004	DM81RKT	Discovery agent	N.A.	Investigative	[13]
PGD2	DMYDW6J	Discovery agent	N.A.	Investigative	[8]
SC-19220	DMU2C9W	Discovery agent	N.A.	Investigative	[3]
SC-51322	DM0LWUV	Discovery agent	N.A.	Investigative	[14]
U46619	DM13FX4	Discovery agent	N.A.	Investigative	[3]
ZK110841	DMY3SUZ	Discovery agent	N.A.	Investigative	[8]
ZM 325802	DMC46RQ	Discovery agent	N.A.	Investigative	[15]

References

• [1] Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.Expert Opin Ther Pat. 2015 Jul;25(7):837-44.
• [2] Effect of lipo-pro-prostaglandin E1, AS-013 on rat inner ear microcirculatory thrombosis. Prostaglandins Leukot Essent Fatty Acids. 1998 Sep;59(3):203-7.
• [3] Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41.
• [4] The prostaglandin E2 receptor-1 (EP-1) mediates acid-induced visceral pain hypersensitivity in humans. Gastroenterology. 2003 Jan;124(1):18-25.
• [5] ONO-8130, a selective prostanoid EP1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis. Pain. 2011 Jun;152(6):1373-81.
• [6] Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP(1) antagonist, on breast cancer development. Carcinogenesis. 2001 Dec;22(12):2001-4.
• [7] The 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.
• [8] Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand binding techniques. J Pharm Pharmacol. 2002 Apr;54(4):539-47.
• [9] The discovery of 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid, GW848687X, a potent and s... Bioorg Med Chem Lett. 2007 Jan 15;17(2):385-9.
• [10] Ligand 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.
• [11] MF498 [N-{[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide], a selective E prostanoid receptor 4 antagonist, relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis. J Pharmacol Exp Ther. 2008 May;325(2):425-34.
• [12] New class of biphenylene dibenzazocinones as potent ligands for the human EP1 prostanoid receptor. Bioorg Med Chem Lett. 1999 Sep 20;9(18):2699-704.
• [13] The 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.
• [14] Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting. J Clin Invest. 2007 Sep;117(9):2496-505.
• [15] Characterization of the prostanoid receptor types involved in mediating calcitonin gene-related peptide release from cultured rat trigeminal neurones. Br J Pharmacol. 2001 Nov;134(6):1296-302.