Details of the Drug Combination

General Information of Drug Combination (ID: DCEVAH6)

• Drug Combination Name: Tenofovir disoproxil + Emtricitabine
• Indication: HIV; Status: Phase 1 [1]
• Component Drugs:
  Tenofovir disoproxil (DM62IPN): N.A.
  Emtricitabine (DMBMUWZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Tenofovir disoproxil Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

Tenofovir disoproxil Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]

Indication(s) of Emtricitabine

Disease Entry	ICD 11	Status	REF
Hepatitis virus infection	1E50-1E51	Approved	[2]
Human immunodeficiency virus infection	1C62	Approved	[2]
Hepatitis B virus infection	1E51.0	Phase 3	[3]

Emtricitabine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Modulator	[2]

Emtricitabine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[6]

Emtricitabine Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Decreases Expression	[7]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[8]
Deoxycytidine kinase (DCK)	OTW8HLZC	DCK_HUMAN	Affects Binding	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Human Immunodeficiency Virus-type 1 Infection	DC688W3	N. A.	Phase 3	[10]
Human Immunodeficiency Virus-type 1 Infection	DC8CXAS	N. A.	Phase 3	[10]
Acute HIV Infection	DC1OKMA	N. A.	Phase 1	[11]
HIV Infection	DCSMP7W	N. A.	Phase 1	[12]

References

• [1] ClinicalTrials.gov (NCT02904369) PK and PD Study of Oral F/TAF for HIV Prevention
• [2] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [3] Clinical pipeline report, company report or official report of Gilead (2011).
• [4] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [5] FDA label of Bictegravir, emtricitabine, and tenofovir alafenamide. The 2020 official website of the U.S. Food and Drug Administration.
• [6] Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters. Xenobiotica. 2017 Jan;47(1):77-85.
• [7] Chronic Nucleoside Reverse Transcriptase Inhibitors Disrupt Mitochondrial Homeostasis and Promote Premature Endothelial Senescence. Toxicol Sci. 2019 Dec 1;172(2):445-456. doi: 10.1093/toxsci/kfz203.
• [8] Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
• [9] Nonenantioselectivity property of human deoxycytidine kinase explained by structures of the enzyme in complex with L- and D-nucleosides. J Med Chem. 2007 Jun 28;50(13):3004-14. doi: 10.1021/jm0700215. Epub 2007 May 27.
• [10] ClinicalTrials.gov (NCT01709084) A Clinical Trial Comparing the Efficacy of Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus TDF/FTC/Efavirenz (TDF/FTC/EFV) in Patients With Undetectable Plasma HIV-1 RNA on Current First-line Treatment
• [11] ClinicalTrials.gov (NCT00734344) Pilot Study of Raltegravir/Truvada Versus Efavirenz/Truvada for Adults With Acute IV-1 Infection
• [12] ClinicalTrials.gov (NCT01505114) Evaluating the Safety and Tolerability of Antiretroviral Drug Regimens Used as Pre-Exposure Prophylaxis to Prevent HIV Infection in At-Risk Men Who Have Sex With Men and in At-Risk Women