Details of the Drug

General Information of Drug (ID: DM2V7U1)

Drug Name
FR-181157
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]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski):
0		 Molecular Weight 487.5
Topological Polar Surface Area Not Available
Rotatable Bond Count 8
Hydrogen Bond Donor Count 0
Hydrogen Bond Acceptor Count 5
Chemical Identifiers
Formula
C30H26NNaO4
IUPAC Name
sodium;2-[3-[[(1S)-2-(4,5-diphenyl-1,3-oxazol-2-yl)cyclohex-2-en-1-yl]methyl]phenoxy]acetate
Canonical SMILES
C1CC=C([C@@H](C1)CC2=CC(=CC=C2)OCC(=O)[O-])C3=NC(=C(O3)C4=CC=CC=C4)C5=CC=CC=C5.[Na+]
InChI
InChI=1S/C30H27NO4.Na/c32-27(33)20-34-25-16-9-10-21(19-25)18-24-15-7-8-17-26(24)30-31-28(22-11-3-1-4-12-22)29(35-30)23-13-5-2-6-14-23;/h1-6,9-14,16-17,19,24H,7-8,15,18,20H2,(H,32,33);/q;+1/p-1/t24-;/m0./s1
InChIKey
DPECFBBZFTXROT-JIDHJSLPSA-M
Cross-matching ID
PubChem CID
23685469
CAS Number
171046-15-4
TTD ID
D0TA0L

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Prostaglandin E2 receptor EP4 (PTGER4) DTT PTGER4 5.27E-01 -0.05 -0.1
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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 Clinical pipeline report, company report or official report of Tempest Therapeutics.
10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11 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.
12 Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol. 1997 Dec 11;340(2-3):227-41.
13 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.
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 BAY x 1005 attenuates atherosclerosis in apoE/LDLR - double knockout mice. J Physiol Pharmacol. 2007 Sep;58(3):583-8.
16 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.
17 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.
18 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.
19 Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J. 2012 Oct;40(4):874-80.
20 Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94.
21 Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J Biol Chem. 2003 Feb 28;278(9):6947-58.
22 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.
23 Prostaglandin I2 IP Receptor Agonist, Beraprost, Prevents Transient Global Cerebral Ischemia Induced Hippocampal CA1 Injury in Aging Mice. J Neurol Disord. 2014;2:1000174.
24 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.
25 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
26 Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. Brain Res. 1997 Sep 26;769(2):321-8.