Details of the Drug

General Information of Drug (ID: DMVPLNC)

Drug Name

Ingrezza

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]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

418.6

Logarithm of the Partition Coefficient (xlogp)

4.3

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.5-1 h []
Bioavailability: The bioavailability of drug is 49% []
Clearance: The clearance of drug is 7.2 L/h []
Elimination: Roughly 60% is excreted in urine and 30% in feces []
Half-life: The concentration or amount of drug in body reduced by one-half in 15 - 22 hours []
Metabolism: The drug is metabolized via oxidation by CYP3A4/5 to a mono-oxidzed metabolite NBI-136110 which also appears to pharmacologically active []
Unbound Fraction: The unbound fraction of drug in plasma is 0.01% [3]
Vd: The volume of distribution (Vd) of drug is 92 L []

Chemical Identifiers

Formula: C24H38N2O4
IUPAC Name: [(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
Canonical SMILES: CC(C)C[C@@H]1CN2CCC3=CC(=C(C=C3[C@H]2C[C@H]1OC(=O)[C@H](C(C)C)N)OC)OC
InChI: InChI=1S/C24H38N2O4/c1-14(2)9-17-13-26-8-7-16-10-21(28-5)22(29-6)11-18(16)19(26)12-20(17)30-24(27)23(25)15(3)4/h10-11,14-15,17,19-20,23H,7-9,12-13,25H2,1-6H3/t17-,19-,20-,23+/m1/s1
InChIKey: GEJDGVNQKABXKG-CFKGEZKQSA-N

Cross-matching ID

PubChem CID: 24795069
CAS Number: 1025504-45-3
DrugBank ID: DB11915
TTD ID: D63WMQ
ACDINA ID: D00715

Repurposed Drugs (RPD)

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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	[4]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Synaptic vesicular amine transporter (SLC18A2)	OTUOMMM6	VMAT2_HUMAN	Gene/Protein Processing	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Tardive dyskinesia

ICD Disease Classification

8A02.10

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Synaptic vesicle amine transporter (SLC18A2)	DTT	SLC18A2	2.69E-02	-0.04	-0.11

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ingrezza (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Ingrezza and Ivosidenib.	Acute myeloid leukaemia [2A60]	[6]
Gilteritinib	DMTI0ZO	Moderate	Increased risk of prolong QT interval by the combination of Ingrezza and Gilteritinib.	Acute myeloid leukaemia [2A60]	[7]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of Ingrezza and Oliceridine.	Acute pain [MG31]	[8]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Ingrezza and Levalbuterol.	Asthma [CA23]	[9]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Ingrezza caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[8]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Ingrezza caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[10]
Ripretinib	DM958QB	Moderate	Decreased clearance of Ingrezza due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[11]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Ingrezza caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[12]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Ingrezza caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[13]
Dacomitinib	DMOH8VY	Major	Decreased metabolism of Ingrezza caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[8]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Ingrezza and Selpercatinib.	Lung cancer [2C25]	[14]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Ingrezza caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[15]
Arry-162	DM1P6FR	Moderate	Decreased clearance of Ingrezza due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[11]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Ingrezza due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[16]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Ingrezza caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[14]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of Ingrezza and Entrectinib.	Non-small cell lung cancer [2C25]	[11]
Rucaparib	DM9PVX8	Moderate	Additive CNS depression effects by the combination of Ingrezza and Rucaparib.	Ovarian cancer [2C73]	[8]
Triclabendazole	DMPWGBR	Moderate	Additive CNS depression effects by the combination of Ingrezza and Triclabendazole.	Parasitic worm infestation [1F90]	[8]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Ingrezza caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[17]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Ingrezza and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[18]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Ingrezza and Lefamulin.	Pneumonia [CA40]	[19]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Ingrezza caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[14]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Ingrezza caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Ingrezza caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[20]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Ingrezza due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[21]
Betrixaban	DM2C4RF	Moderate	Decreased clearance of Ingrezza due to the transporter inhibition by Betrixaban.	Venous thromboembolism [BD72]	[22]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
FD&C blue no. 1	E00263	19700	Colorant
Isomalt	E00383	88735	Binding agent; Coating agent; Diluent; Flavoring agent; Suspending agent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Valbenazine 40 mg capsule	40 mg	Oral Capsule	Oral
Valbenazine 80 mg capsule	80 mg	Oral Capsule	Oral
Valbenazine Tosylate 40mg capsule	40mg	Capsule	Oral
Valbenazine Tosylate 80mg capsule	80mg	Capsule	Oral

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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	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine). Prog Med Chem. 2018;57(1):87-111.
5	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.
6	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
7	Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
8	Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
9	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
10	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
11	Cerner Multum, Inc. "Australian Product Information.".
12	Product Information. Givlaari (givosiran). Alnylam Pharmaceuticals, Cambridge, MA.
13	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
14	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
16	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
17	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
18	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
19	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
20	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
21	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
22	Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.