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

General Information of Drug (ID: DMVO1C0)

• Drug Name: NBI-98854 Drug Info
• Synonyms: NBI-98782; Vesicular monoamine transporter 2 inhibitor (CNS indications), Neurocrine; VMAT-2 inhibitor (CNS disease), Neurocrine

Indication

Disease Entry	ICD 11	Status	REF
Movement disorder	8A07-8A0Z	Phase 3	[1]
Tourette syndrome	8A05.00	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 123836
  CAS Number: CAS 3466-75-9
  TTD Drug ID: DMVO1C0
  VARIDT Drug ID: DR01064
  INTEDE Drug ID: DR1665

Molecule-Related Drug Atlas

Drug(s) Targeting Synaptic vesicle amine transporter (SLC18A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Deutetrabenazine	DMUPFLI	Huntington disease	8A01.10	Approved	[5]
Reserpine	DM6VM38	Hypertension	BA00-BA04	Approved	[6]
Tetrabenazine	DMYWQ0O	Huntington disease	8A01.10	Approved	[6]
Alseroxylon	DMB47TQ	Hypertension	BA00-BA04	Approved	[7]
Valbenazine Tosylate	DMQSA2V	Tardive dyskinesia	8A02.10	Approved	[5]
Alkavervir	DMB4HFI	High blood pressure	BA00	Approved	[5]
Ingrezza	DMVPLNC	Tardive dyskinesia	8A02.10	Phase 4	[8]
AV 133	DM0EQ9X	Alzheimer disease	8A20	Phase 3	[9]
Lobeline	DMT3KB4	Substance use disorder	6C4Z	Phase 2	[10]
SOM3355	DMKCBSM	Huntington disease	8A01.10	Phase 2	[2]

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	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[16]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[17]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[18]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[19]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Synaptic vesicle amine transporter (SLC18A2)	TTNZRI3	VMAT2_HUMAN	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[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: 8694).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Mov Disord. 2015 Oct;30(12):1681-7.
• [4] Tardive dyskinesia: placing vesicular monoamine transporter type 2 (VMAT2) inhibitors into clinical perspective. Expert Rev Neurother. 2018 Apr;18(4):323-332.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci. 2009 Jul 1;29(26):8530-8.
• [7] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [8] VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine). Prog Med Chem. 2018;57(1):87-111.
• [9] Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET. PLoS One. 2013 Sep 30;8(9):e75952.
• [10] Design, synthesis and interaction at the vesicular monoamine transporter-2 of lobeline analogs: potential pharmacotherapies for the treatment of psychostimulant abuse. Curr Top Med Chem. 2011;11(9):1103-27.
• [11] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [12] 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.
• [13] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [18] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [19] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [20] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.