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

General Information of Drug (ID: DMVPLNC)

• Drug Name: Ingrezza Drug Info
• Synonyms: Valbenazine; 1025504-45-3; UNII-54K37P50KH; Valbenazine free base; NBI 98854; 54K37P50KH; 1025504-45-3 (free base); (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl L-valinate; L-Valine, (2R,3R,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-yl ester; Valbenazine [USAN:INN]; L-Valine, (2R,3R,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo(a)quinolizin-2-yl ester; ValbenazineNBI-98854; Valbenazine (USAN/INN); GTPL8694; CHEMBL2364639; SCHEMBL15932979; EX-A2002; MFCD28963976; ZINC43195697; CS-5908; DB11915; SB17456; NCGC00522306-02; [(2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl] (2S)-2-amino-3-methylbutanoate; AC-30929; AS-35294; HY-16771; D10675; NBI-98854;NBI98854;NBI 98854; Q27089118; (2R,3R,11bR)-9,10-Dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydro-2H- benzo(a)quinolizin-2-yl L-valinate; (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester; [(2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-yl] (2S)-2-amino-3-methylbutanoate; Valine 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo(a)quinolizin-2-yl ester

Indication

Disease Entry	ICD 11	Status	REF
Tardive dyskinesia	8A02.10	Phase 4	[1]
Tourette syndrome	8A05.00	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 24795069
  CAS Number: CAS 1025504-45-3
  TTD Drug ID: DMVPLNC
  ACDINA Drug ID: D00715

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]
NBI-98854	DMVO1C0	Movement disorder	8A07-8A0Z	Phase 3	[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	[11]

Drug(s) Affected By Synaptic vesicular amine transporter (SLC18A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[12]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[12]
Methamphetamine	DMPM4SK	Anxiety		Approved	[13]
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[14]
Haloperidol	DM96SE0	Delirium		Approved	[14]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Dextroamphetamine	DMMIHVP	Attention deficit hyperactivity disorder	6A05.Z	Approved	[14]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[17]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[18]

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	Antagonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Synaptic vesicular amine transporter (SLC18A2)	OTUOMMM6	VMAT2_HUMAN	Gene/Protein Processing	[4]

References

• [1] ClinicalTrials.gov (NCT03698331) The Potential for Clinical Dependence and Withdrawal Symptoms Associated With Valbenazine. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT03732534) Rollover Study for Continuing NBI-98854 Administration in Pediatric Subjects With Tourette Syndrome. U.S. National Institutes of Health.
• [3] VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine). Prog Med Chem. 2018;57(1):87-111.
• [4] Valbenazine in the treatment of tardive dyskinesia. Neurodegener Dis Manag. 2019 Apr;9(2):73-81. doi: 10.2217/nmt-2019-0001. Epub 2019 Feb 6.
• [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] 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.
• [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] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] The effect of rare human sequence variants on the function of vesicular monoamine transporter 2. Pharmacogenetics. 2004 Sep;14(9):587-94. doi: 10.1097/00008571-200409000-00003.
• [13] Assessing Vesicular Monoamine Transport and Toxicity Using Fluorescent False Neurotransmitters. Chem Res Toxicol. 2021 May 17;34(5):1256-1264. doi: 10.1021/acs.chemrestox.0c00380. Epub 2020 Dec 30.
• [14] Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. doi: 10.1016/0169-328x(94)90050-7.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [17] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [18] Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users. Am J Psychiatry. 2003 Jan;160(1):47-55. doi: 10.1176/appi.ajp.160.1.47.