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

General Information of Drug (ID: DMJPSIL)

• Drug Name: Dapivirine Drug Info
• Synonyms: Dapivirinum; R 147681; R147681; TMC 120; TMC120; GEL-002; R-147681; TMC-120; TMC120-R147681; TMC-120/R-147681; 4-((4-((2,4,6-Trimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile; 4-({4-[(2,4,6-Trimethylphenyl)amino]pyrimidin-2-yl}amino)benzenecarbonitrile; 4-[4-(2,4,6-TRIMETHYL-PHENYLAMINO)-PYRIMIDIN-2-YLAMINO]-BENZONITRILE; 4-[[4-(2,4,6-trimethylanilino)pyrimidin-2-yl]amino]benzonitrile

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Phase 1/2	[1]

• Cross-matching ID:
  PubChem CID: 214347
  CAS Number: CAS 244767-67-7
  TTD Drug ID: DMJPSIL
  INTEDE Drug ID: DR1822

Molecule-Related Drug Atlas

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[3]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[4]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[5]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[7]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[8]
Mycophenolate mofetil	DMPQAGE	Organ transplant rejection	NE84	Approved	[9]
Metronidazole	DMTIVEN	Amoebiasis	1A36	Approved	[10]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[11]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[12]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[16]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[17]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[20]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[21]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[16]

Drug(s) Targeting Human immunodeficiency virus Reverse transcriptase (HIV RT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[23]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[24]
Tenofovir	DM1IS6U	Human immunodeficiency virus infection	1C62	Approved	[22]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[25]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[26]
Delavirdine	DM3NF5G	Human immunodeficiency virus infection	1C62	Approved	[25]
Efavirenz	DMC0GSJ	Human immunodeficiency virus infection	1C62	Approved	[25]
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[1]
Etravirine	DMGV8QU	Human immunodeficiency virus-1 infection	1C62	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[2]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[2]

References

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• [2] Metabolism Of Antiretroviral Drugs Used In Hiv Preexposure Prophylaxis
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• [4] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
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• [6] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [7] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [8] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
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• [10] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [11] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [12] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
• [13] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [14] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [15] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [16] Drug Interactions Flockhart Table
• [17] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [18] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [19] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [20] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [21] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
• [22] Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
• [23] HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.Nat Struct Mol Biol.2012 Jan 22;19(2):253-9.
• [24] A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model. J Biomol Struct Dyn. 1998 Oct;16(2):347-54.
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [26] Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only Curr HIV Res. 2009 May;7(3):320-6.
• [27] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.