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

General Information of Drug (ID: DMG9B1U)

• Drug Name: Elvitegravir Drug Info
• Synonyms: EVG

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[1]

• Cross-matching ID:
  PubChem CID: 5277135
  ChEBI ID: CHEBI:72289
  CAS Number: CAS 697761-98-1
  TTD Drug ID: DMG9B1U
  INTEDE Drug ID: DR0570
  ACDINA Drug ID: D00227

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Integrase (HIV IN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dolutegravir	DMCZGRE	Human immunodeficiency virus infection	1C62	Approved	[1]
Raltegravir	DMYURI6	Human immunodeficiency virus infection	1C62	Approved	[4]
Bictegravir, emtricitabine and tenofovir alafenamide	DMG0H8K	Human immunodeficiency virus infection	1C62	Approved	[5]
GSK1265744	DMT8J0I	Human immunodeficiency virus infection	1C62	Phase 3	[6]
S-1360	DM9KTSG	Human immunodeficiency virus infection	1C62	Phase 2	[7]
S-364735	DMU7ZMH	Human immunodeficiency virus infection	1C62	Phase 2	[8]
C-2507	DMOFT1V	Human immunodeficiency virus infection	1C62	Phase 1	[9]
Acriflavine	DMKVE8X	Human immunodeficiency virus infection	1C62	Phase 1	[10]
S-265744 LAP	DMDQRWT	Human immunodeficiency virus infection	1C62	Phase 1	[11]
VH4524184	DM1FS0F	Human immunodeficiency virus infection	1C62	Phase 1	[12]

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	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

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	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[28]
Metronidazole	DMTIVEN	Abscess		Approved	[29]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[30]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[3]

References

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• [2] FDA Label of Elvitegravir. The 2020 official website of the U.S. Food and Drug Administration.
• [3] Elvitegravir for the treatment of HIV infection. Drugs Today (Barc). 2014 Mar;50(3):209-17.
• [4] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [5] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [6] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [7] HIV-1 integrase inhibitors: an emerging clinical reality. Drugs R D. 2007;8(3):155-68.
• [8] The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral. Antimicrob Agents Chemother. 2008 Mar;52(3):901-8.
• [9] Elvitegravir: a new HIV integrase inhibitor. Antivir Chem Chemother. 2009 Oct 19;20(2):79-85.
• [10] Why have ten or so nontoxic, retrovirus integrase inhibitors not been made available for AIDS treatment. Biomed Pharmacother. 1999 Dec;53(10):484-6.
• [11] Long-acting shot prevents infection with HIV analogue. Nature. doi:10.1038/nature.2014.14819. 04 March 2014
• [12] Clinical pipeline report, company report or official report of ViiV Healthcare
• [13] 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.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] 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.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] 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.
• [18] 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.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] 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.
• [21] 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.
• [22] Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
• [23] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
• [24] Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [29] 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.
• [30] 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.
• [31] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.