Details of the Drug

General Information of Drug (ID: DMT4VSE)

• Drug Name: BMS-181101
• Synonyms: 1H-Indole

Indication

Disease Entry	ICD 11	Status	REF
Mood disorder	6A60-6E23	Discontinued in Phase 2	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 369.4
  Topological Polar Surface Area (xlogp); 3
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C20H24FN5O
  IUPAC Name: 5-fluoro-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1H-indole
  Canonical SMILES: COC1=CN=CN=C1N2CCN(CC2)CCCC3=CNC4=C3C=C(C=C4)F
  InChI: InChI=1S/C20H24FN5O/c1-27-19-13-22-14-24-20(19)26-9-7-25(8-10-26)6-2-3-15-12-23-18-5-4-16(21)11-17(15)18/h4-5,11-14,23H,2-3,6-10H2,1H3
  InChIKey: NRLXAYBZNVHRFL-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 177836
  CAS Number: 141071-67-2
  TTD ID: D00QXV
  INTEDE ID: DR1783

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Antagonist	[3], [4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[5]

References

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• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005177)
• [3] Sensitive triple-quadrupole mass spectrometric assay for the determination of BMS-181885, a 5-HT1 agonist, in human plasma following solid phase extraction. Biomed Chromatogr. 1999 Oct;13(6):425-30.
• [4] Sustained pain relief with dihydroergotamine in migraine is potentially due to persistent binding to 5-HT1B and 5-HT1D receptors. . The Journal of Headache and Pain 201314(Suppl 1):P75.
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• [14] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [15] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [16] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [17] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [18] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [19] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [20] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [21] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [22] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [23] Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
• [24] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [25] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [26] An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
• [27] Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clin Ther. 2001 Nov;23(11):1867-75.
• [28] Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
• [29] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [30] Company report (NeurAxon)