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

General Information of Drug (ID: DMJYDVK)

• Drug Name: Cariprazine Drug Info
• Synonyms: Cariprazine; 839712-12-8; RGH-188; RGH 188; Cariprazine(RGH188); UNII-F6RJL8B278; F6RJL8B278; CHEMBL3085826; 3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea; Cariprazine [USAN:INN]; Reagila; MP-214; MP 214; Cariprazine (USAN/INN); Cariprazine (RGH-188); C21H32Cl2N4O; SCHEMBL184342; SCHEMBL184343; GTPL7671; SCHEMBL7861573; CHEMBL2028019; CHEBI:90933; HSDB 8310; DTXSID80232867; KPWSJANDNDDRMB-QAQDUYKDSA-N; MolPort-039-139-594; BDBM263449; BCP14691; BDBM50443101; BDBM50382290; ZINC38309313; 3526AH

Indication

Disease Entry	ICD 11	Status	REF
Bipolar disorder	6A60	Approved	[1]

• Cross-matching ID:
  PubChem CID: 11154555
  ChEBI ID: CHEBI:90933
  CAS Number: CAS 839712-12-8
  TTD Drug ID: DMJYDVK
  INTEDE Drug ID: DR0276
  ACDINA Drug ID: D00100

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D3 receptor (D3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pramipexole	DMNMW9R	Parkinson disease	8A00.0	Approved	[4]
Ropinirole	DMA6S1D	Parkinson disease	8A00.0	Approved	[4]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[5]
P2B-001	DM9PVHX	Parkinson disease	8A00.0	Phase 3	[6]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[7]
ONC201	DMM5SCF	Endometrial cancer	2C76	Phase 2	[8]
TAK-906	DMBQD9H	Diabetic gastroparesis	DA41.00	Phase 2	[9]
GSK598809	DMGU05N	Drug abuse	6C4G.1Z	Phase 2	[10]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[10]
Pfizer 10	DM6ER9L	Female sexual arousal dysfunction	HA01.1	Phase 1	[11]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[12]
Haloperidol	DM96SE0	Delirium		Approved	[13]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[14]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[15]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[16]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[17]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[18]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[19]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[20]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[21]

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	[22]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[23]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[24]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[25]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[28]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[29]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[23]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[30]

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	[31]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[32]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[33]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[34]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[35]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[36]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[37]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Modulator	[2]
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	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: 7671).
• [2] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [3] Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):193-206.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [6] Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Safety, Pharmacokinetics, and Pharmacodynamics of Trazpiroben (TAK-906), a Novel Selective D 2 /D 3 Receptor Antagonist: A Phase 1 Randomized, Placebo-Controlled Single- and Multiple-Dose Escalation Study in Healthy Participants. Clin Pharmacol Drug Dev. 2021 Jan 18.
• [10] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [11] Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66.
• [12] The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
• [13] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [14] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [15] Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
• [16] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [17] 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: 3639).
• [18] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [19] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [20] Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
• [21] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [22] 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.
• [23] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [24] 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.
• [25] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [26] 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.
• [27] 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.
• [28] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [29] 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.
• [30] 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.
• [31] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [32] 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.
• [33] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [34] 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.
• [35] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [36] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [37] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [38] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.