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

General Information of Drug (ID: DMT4VSE)

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

Indication

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

• Cross-matching ID:
  PubChem CID: 177836
  CAS Number: CAS 141071-67-2
  TTD Drug ID: DMT4VSE
  INTEDE Drug ID: DR1783

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 1D receptor (HTR1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[4]
Eletriptan	DMW649X	Migraine	8A80	Approved	[5]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[5]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[5]
Sumatriptan	DMVYXR8	Cluster headache	8A81.0	Approved	[6]
Rizatriptan	DMDJMA3	Migraine	8A80	Approved	[7]
Almogran	DM7I64Z	Migraine	8A80	Approved	[8]
Neu-P11	DMIQDFW	Alzheimer disease	8A20	Phase 2	[9]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[10]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[11]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[21]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[24]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[25]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[26]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[27]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[28]

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	[2]

Drug-Metabolizing Enzyme (DME)

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

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: 108).
• [2] 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.
• [3] Pharmacokinetic assessment of the sites of first-pass metabolism of BMS-181101, an antidepressant agent, in rats. J Pharm Pharmacol. 1998 Mar;50(3):275-8.
• [4] Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [7] An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
• [8] 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.
• [9] Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Company report (NeurAxon)
• [12] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [13] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [14] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [15] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [16] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [17] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [18] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [19] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [20] 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.
• [21] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [22] 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.
• [23] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [24] 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.
• [25] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [26] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [27] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [28] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.