Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM2V7U1)

• Drug Name: FR-181157 Drug Info
• Synonyms: SCHEMBL7960020; GTPL5854; FR181157; FR 181157; 2-[3-[[2-[4,5-di(phenyl)-1,3-oxazol-2-yl]-1-cyclohex-2-enyl]methyl]phenoxy]acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 23685469
  CAS Number: CAS 171046-15-4
  TTD Drug ID: DM2V7U1

Molecule-Related Drug Atlas

Drug(s) Targeting Prostaglandin E2 receptor EP4 (PTGER4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
16,16-dimethyl-PGE2	DMNF38S	Stem cell engraftment	QB63.8	Phase 2	[5]
RQ-00000007 (oral)	DMMYTRU	Pain	MG30-MG3Z	Phase 2	[6]
ONO-AE1-437	DMCUGI8	Asthma	CA23	Phase 2	[7]
BGC-20-1531	DMS2MQ5	Migraine	8A80	Phase 2	[8]
IK-007	DMBLFPN	Non-small-cell lung cancer	2C25	Phase 1/2	[9]
TPST-1495	DM3GSB2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
E7046	DMFVT43	Rectal adenocarcinoma	2B92	Phase 1	[11]
ONO-4232	DMO4SD2	Acute heart failure	BD10-BD13	Phase 1	[12]
ONO-4578	DME63VK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
AN0025	DMGSYPY	Aggressive cancer	2A00-2F9Z	Phase 1	[13]

Drug(s) Targeting Prostaglandin E2 receptor EP3 (PTGER3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
16,16-dimethyl-PGE2	DMNF38S	Stem cell engraftment	QB63.8	Phase 2	[5]
ONO-9054	DM5O6GC	Glaucoma/ocular hypertension	9C61	Phase 2	[14]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[5]
BUTAPROST	DMVYNJZ	Discovery agent	N.A.	Patented	[15]
DG041	DMVO9WM	Peripheral vascular disease	BD4Z	Discontinued in Phase 2	[16]
GR-63799X	DM13GK8	Asthma	CA23	Discontinued in Phase 1	[17]
U46619	DM13FX4	Discovery agent	N.A.	Investigative	[18]
carbacyclin	DMMBQYE	Discovery agent	N.A.	Investigative	[5]
PGD2	DMYDW6J	Discovery agent	N.A.	Investigative	[19]
butaprost (free acid form)	DM5MZHP	Discovery agent	N.A.	Investigative	[18]

Drug(s) Targeting Prostacyclin receptor (PTGIR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Treprostinil	DMTIQF3	Pulmonary arterial hypertension	BB01.0	Approved	[20]
Selexipag	DMAHSU0	Pulmonary arterial hypertension	BB01.0	Approved	[21]
Epoprostenol	DMUTYR2	Allergic rhinitis	CA08.0	Approved	[22]
Dinoprost Tromethamine	DMXQKSL	Abortion	JA00	Approved	[23]
Misoprostol	DMHVJFK	Medical abortion	JA00.1Z	Approved	[23]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[24]
Beraprost	DML634R	Pulmonary hypertension	BB01	Phase 4	[25]
esuberaprost	DMXLGED	Gout	FA25	Phase 3	[26]
Ralinepag	DM7G4Y9	Pulmonary arterial hypertension	BB01.0	Phase 2	[27]
Clinprost	DM6E5VA	Asthma	CA23	Discontinued in Preregistration	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostacyclin receptor (PTGIR)	TTOFYT1	PI2R_HUMAN	Inhibitor	[2]
Prostaglandin E2 receptor EP3 (PTGER3)	TTPNGDE	PE2R3_HUMAN	Inhibitor	[3]
Prostaglandin E2 receptor EP4 (PTGER4)	TT79WV3	PE2R4_HUMAN	Inhibitor	[4]

References

• [1] URL: 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: 5854).
• [2] Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4861-4.
• [3] Metabolism investigation leading to novel drug design: orally active prostacyclin mimetics. Part 4. Bioorg Med Chem Lett. 2005 Jul 1;15(13):3284-7.
• [4] Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective human prostaglandin EP(4) receptor antagonists. J Med Chem. 2005 May 5;48(9):3103-6.
• [5] 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.
• [6] Clinical pipeline report, company report or official report of Avarx.
• [7] An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo. Pediatr Res. 2004 Oct;56(4):586-90.
• [8] BGC20-1531, 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.
• [9] Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation. Vet Med Sci. 2015 Dec 21;2(1):3-9.
• [10] Clinical pipeline report, company report or official report of Tempest Therapeutics.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] ONO-4232, an EP4-selective Agonist, Improves Left Ventricular Diastolic Dysfunction and Ameliorates Acute and Chronic Heart Failure in Animal Models. Circulation. 2012; 126: A15345.
• [13] AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer. Radiother Oncol. 2023 Aug;185:109669.
• [14] IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2547-52.
• [15] 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.
• [16] BAY x 1005 attenuates atherosclerosis in apoE/LDLR - double knockout mice. J Physiol Pharmacol. 2007 Sep;58(3):583-8.
• [17] Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat. Br J Pharmacol. 1999 Feb;126(4):849-58.
• [18] 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.
• [19] Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41.
• [20] Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J. 2009 Apr;157(4):625-35.
• [21] Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80.
• [22] Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94.
• [23] Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J Biol Chem. 2003 Feb 28;278(9):6947-58.
• [24] Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
• [25] Prostaglandin I2 IP Receptor Agonist, Beraprost, Prevents Transient Global Cerebral Ischemia Induced Hippocampal CA1 Injury in Aging Mice. J Neurol Disord. 2014;2:1000174.
• [26] Specific binding of the new stable epoprostenol analogue beraprost sodium to prostacyclin receptors on human and rat platelets. Arzneimittelforschung. 1989 Apr;39(4):495-9.
• [27] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [28] Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. Brain Res. 1997 Sep 26;769(2):321-8.