Details of the Drug Combination

General Information of Drug Combination (ID: DC2A9FF)

• Drug Combination Name: Emtricitabine + Tenofovir alafenamide
• Indication: Human immunodeficiency virus-1 infection; Status: Phase 1 [1]
• Component Drugs:
  Emtricitabine (DMBMUWZ): Small molecular drug
  Tenofovir alafenamide (DMTQF4A): N.A.

Molecular Interaction Atlas of This Drug Combination

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	[5]

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	[6]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[7]
Deoxycytidine kinase (DCK)	OTW8HLZC	DCK_HUMAN	Affects Binding	[8]

Indication(s) of Tenofovir alafenamide

Disease Entry	ICD 11	Status	REF
HIV infectious disease	N.A.	Approved	[4]

Tenofovir alafenamide Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]

Tenofovir alafenamide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cathepsin A (CTSA)	DE14JZK	PPGB_HUMAN	Metabolism	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
HIV	DCZ4OHF	N. A.	Phase 3	[12]
Human immunodeficiency virus-1 infection	DCJIOQC	N. A.	Phase 1	[1]
HIV	DCA6JSD	N. A.	Phase 1	[13]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [3] Clinical pipeline report, company report or official report of Gilead (2011).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters. Xenobiotica. 2017 Jan;47(1):77-85.
• [6] 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.
• [7] Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
• [8] 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.
• [9] Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472.
• [10] FDA label of Bictegravir, emtricitabine, and tenofovir alafenamide. The 2020 official website of the U.S. Food and Drug Administration.
• [11] Bictegravir/Emtricitabine/Tenofovir Alafenamide: a review in HIV-1 infection. Drugs. 2018 Nov;78(17):1817-1828.
• [12] ClinicalTrials.gov (NCT05979311) A Study to Evaluate the Efficacy, Safety, and Tolerability of Using an Oral Once-daily 2 Drug Regimen Compared to an Oral Once-daily 3 Drug Regimen for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Adults Who Have Not Previously Taken Antiretroviral Therapy
• [13] ClinicalTrials.gov (NCT02904369) PK and PD Study of Oral F/TAF for HIV Prevention