Details of the Drug

General Information of Drug (ID: DMHG57U)

Drug Name

OPC-34712

Synonyms

Brexpiprazole

Indication

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

433.6

Logarithm of the Partition Coefficient (xlogp)

4.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Clearance: The clearance of drug is 19.8 mL/h/kg []
Half-life: The concentration or amount of drug in body reduced by one-half in 3411 hours [3]
Metabolism: The drug is metabolized via the CYP3A4 and CYP2D6 enzymes into its major metabolite, DM-3411 []
Unbound Fraction: The unbound fraction of drug in plasma is 0.002% [3]
Vd: The volume of distribution (Vd) of drug is 1.56 L/kg []

Chemical Identifiers

Formula: C25H27N3O2S
IUPAC Name: 7-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy]-1H-quinolin-2-one
Canonical SMILES: C1CN(CCN1CCCCOC2=CC3=C(C=C2)C=CC(=O)N3)C4=C5C=CSC5=CC=C4
InChI: InChI=1S/C25H27N3O2S/c29-25-9-7-19-6-8-20(18-22(19)26-25)30-16-2-1-11-27-12-14-28(15-13-27)23-4-3-5-24-21(23)10-17-31-24/h3-10,17-18H,1-2,11-16H2,(H,26,29)
InChIKey: ZKIAIYBUSXZPLP-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 11978813
ChEBI ID: CHEBI:134716
CAS Number: 913611-97-9
DrugBank ID: DB09128
TTD ID: D0P0OU
VARIDT ID: DR01335
INTEDE ID: DR0227
ACDINA ID: D00076

Combinatorial Drugs (CBD)

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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
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Modulator	[4]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Modulator	[4]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Sodium-dependent dopamine transporter (SLC6A3)	DT3BA8L	SC6A3_HUMAN	Substrate	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Gene/Protein Processing	[7]
ATP-citrate synthase (ACLY)	OTRL9ZRP	ACLY_HUMAN	Gene/Protein Processing	[7]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Gene/Protein Processing	[7]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Gene/Protein Processing	[7]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Gene/Protein Processing	[7]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Gene/Protein Processing	[7]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Gene/Protein Processing	[7]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Gene/Protein Processing	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Major depressive disorder

ICD Disease Classification

6A70.3

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
5-HT 1A receptor (HTR1A)	DTT	HTR1A	1.49E-05	-0.22	-0.58
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49
Sodium-dependent dopamine transporter (SLC6A3)	DTP	DAT1	2.11E-01	1.59E-02	5.57E-02
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

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 OPC-34712 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Major	Additive CNS depression effects by the combination of OPC-34712 and Oliceridine.	Acute pain [MG31]	[8]
Phenyltoloxamine	DMKAEQW	Moderate	Additive anticholinergic effects by the combination of OPC-34712 and Phenyltoloxamine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[9]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of OPC-34712 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[10]
Tucatinib	DMBESUA	Major	Decreased metabolism of OPC-34712 caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[10]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of OPC-34712 caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[11]
MK-8228	DMOB58Q	Major	Decreased metabolism of OPC-34712 caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[10]
Deutetrabenazine	DMUPFLI	Major	Increased risk of prolong QT interval by the combination of OPC-34712 and Deutetrabenazine.	Dystonic disorder [8A02]	[12]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of OPC-34712 caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[13]
Levamlodipine	DM92S6N	Moderate	Additive hypotensive effects by the combination of OPC-34712 and Levamlodipine.	Hypertension [BA00-BA04]	[14]
Givosiran	DM5PFIJ	Major	Decreased metabolism of OPC-34712 caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[10]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of OPC-34712 and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[15]
Berotralstat	DMWA2DZ	Major	Decreased metabolism of OPC-34712 caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[10]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of OPC-34712 and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[16]
Brigatinib	DM7W94S	Moderate	Increased metabolism of OPC-34712 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[17]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of OPC-34712 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[18]
Dacomitinib	DMOH8VY	Major	Decreased metabolism of OPC-34712 caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[10]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of OPC-34712 caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[19]
IPI-145	DMWA24P	Major	Decreased metabolism of OPC-34712 caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[10]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of OPC-34712 and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[20]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of OPC-34712 and Lasmiditan.	Migraine [8A80]	[21]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of OPC-34712 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[10]
Rolapitant	DM8XP26	Moderate	Decreased metabolism of OPC-34712 caused by Rolapitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[22]
Rucaparib	DM9PVX8	Major	Decreased metabolism of OPC-34712 caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[10]
Opicapone	DM1BKA6	Moderate	Additive CNS depression effects by the combination of OPC-34712 and Opicapone.	Parkinsonism [8A00]	[23]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of OPC-34712 caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[24]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of OPC-34712 and Methylscopolamine.	Peptic ulcer [DA61]	[15]
Lefamulin	DME6G97	Moderate	Decreased metabolism of OPC-34712 caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[25]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of OPC-34712 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[26]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of OPC-34712 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[19]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of OPC-34712 caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[27]
LEE011	DMMX75K	Major	Decreased metabolism of OPC-34712 caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[10]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of OPC-34712 caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[28]
Acrivastine	DMTIGA0	Moderate	Additive anticholinergic effects by the combination of OPC-34712 and Acrivastine.	Vasomotor/allergic rhinitis [CA08]	[15]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Brexpiprazole 0.25 mg tablet	0.25 mg	Oral Tablet	Oral
Brexpiprazole 0.5 mg tablet	0.5 mg	Oral Tablet	Oral
Brexpiprazole 2 mg tablet	2 mg	Oral Tablet	Oral
Brexpiprazole 3 mg tablet	3 mg	Oral Tablet	Oral
Brexpiprazole 1 mg tablet	1 mg	Oral Tablet	Oral
Brexpiprazole 4 mg tablet	4 mg	Oral Tablet	Oral

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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: 7672).
2	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
5	Brexpiprazole reduces hyperactivity, impulsivity, and risk-preference behavior in mice with dopamine transporter knockdown-a model of mania. Psychopharmacology (Berl). 2017 Mar;234(6):1017-1028.
6	Brexpiprazole: first global approval. Drugs. 2015 Sep;75(14):1687-97.
7	Brexpiprazole suppresses cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in colorectal cancer. Environ Toxicol. 2023 Oct;38(10):2352-2360. doi: 10.1002/tox.23871. Epub 2023 Jun 22.
8	US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
9	Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82. [PMID: 7202232]
10	Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
11	Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
12	Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
13	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
14	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
15	Cohen MA, Alfonso CA, Mosquera M. Development of urinary retention during treatment with clozapine and meclizine [published correction appears in Am J Psychiatry 1994 Jun;151(6):952]. Am J Psychiatry. 1994;151(4):619-620. [PMID: 8147469]
16	Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
17	Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
18	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
19	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
20	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
21	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
22	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
23	Mims RB, Scott CL, Modebe O, Bethune JE "Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine." J Clin Endocrinol Metab 40 (1975): 256-9. [PMID: 1117978]
24	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
25	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
26	Product Information. Oxbryta (voxelotor). Global Blood Therapeutics, Inc., South San Francisco, CA.
27	Cerner Multum, Inc. "Australian Product Information.".
28	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.