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

General Information of Drug (ID: DMSEVBH)

• Drug Name: Lersivirine Drug Info
• Synonyms: cc-718; Lersivirine (UK-453061)

Indication

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

• Cross-matching ID:
  PubChem CID: 16739244
  CAS Number: CAS 473921-12-9
  TTD Drug ID: DMSEVBH
  INTEDE Drug ID: DR1825

Molecule-Related Drug Atlas

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	[4]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[5]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[6]
Tenofovir	DM1IS6U	Chronic hepatitis B virus infection		Approved	[4]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[7]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[8]
Delavirdine	DM3NF5G	Human immunodeficiency virus infection	1C62	Approved	[7]
Efavirenz	DMC0GSJ	Human immunodeficiency virus infection	1C62	Approved	[7]
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[9]
Etravirine	DMGV8QU	Human immunodeficiency virus-1 infection	1C62	Approved	[10]

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	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]

Drug(s) Metabolized By UDP-glucuronosyltransferase 2B7 (UGT2B7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[23]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[19]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[24]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[25]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[26]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	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	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT01254656) A Long Term Safety Study Of Lersivirine For The Treatment Of HIV-1 Infection In Subjects Who Have Completed Treatment With Lersivirine In Studies A5271015 And A5271022. U.S. National Institutes of Health.
• [2] Safety and tolerability of lersivirine, a nonnucleoside reverse transcriptase inhibitor, during a 28-day, randomized, placebo-controlled, Phase I clinical study in healthy male volunteers. Clin Ther.2010 Oct;32(11):1889-95.
• [3] Excretion and metabolism of lersivirine (5-{[3,5-diethyl-1-(2-hydroxyethyl)(3,5-14C2)-1H-pyrazol-4-yl]oxy}benzene-1,3-dicarbonitrile), a next-generation non-nucleoside reverse transcriptase inhibitor, after administration of [14C]Lersivirine to healthy volunteers. Drug Metab Dispos. 2010 May;38(5):789-800.
• [4] Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
• [5] 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.
• [6] 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.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] 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.
• [9] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [10] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [11] 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.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] 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.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] 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.
• [16] 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.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] 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.
• [19] 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.
• [20] Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
• [21] Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultra-performance liquid chromatography with MS detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):84-90.
• [22] Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
• [23] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [24] Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
• [25] Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
• [26] Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
• [27] Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.