Details of the Drug Combination

General Information of Drug Combination (ID: DCFVOSL)

Drug Combination Name
Tenofovir Dolutegravir
Indication
Disease Entry Status REF
Human Immunodeficiency Virus Phase 3 [1]
Component Drugs Tenofovir   DM1IS6U Dolutegravir   DMCZGRE
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Tenofovir
Disease Entry ICD 11 Status REF
Chronic hepatitis B virus infection N.A. Approved [2]
Hepatitis B virus infection 1E51.0 Approved [2]
Human immunodeficiency virus infection 1C62 Approved [3]
Tenofovir 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 Inhibitor [5]
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Tenofovir Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [8]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [9]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]
Multidrug resistance-associated protein 7 (ABCC10) DTPS120 MRP7_HUMAN Substrate [11]
Multidrug resistance-associated protein 8 (ABCC11) DTWN7FC ABCCB_HUMAN Substrate [12]
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⏷ Show the Full List of 7 DTP(s)
Indication(s) of Dolutegravir
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [4]
Dolutegravir Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human immunodeficiency virus Integrase (HIV IN) TT5FH9Y POL_HV1B1 Modulator [13]
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Dolutegravir Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
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Dolutegravir Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [15]
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Dolutegravir Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 26A1 (CYP26A1) OTL1DFWV CP26A_HUMAN Decreases Expression [16]
T-box transcription factor TBX6 (TBX6) OTW1Q8RM TBX6_HUMAN Increases Expression [16]
Homeobox protein Hox-B1 (HOXB1) OTGC0EKI HXB1_HUMAN Increases Expression [16]
Fibroblast growth factor 8 (FGF8) OTFU0IUW FGF8_HUMAN Increases Expression [16]
Homeobox protein MIXL1 (MIXL1) OT584VOQ MIXL1_HUMAN Increases Expression [16]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
HIV Infections DCTL991 N. A. Phase 2 [17]
AIDS DCVH2RE N. A. Phase 1 [18]
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References

1 ClinicalTrials.gov (NCT03988452) Nucleosides And Darunavir/Dolutegravir In Africa
2 Tenofovir FDA Label
3 Anti-hepatitis B virus activity in vitro of combinations of tenofovir with nucleoside/nucleotide analogues. Antivir Chem Chemother. 2009;19(4):165-76.
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7365).
5 Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
6 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
7 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
8 Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol. 2007 Feb;71(2):619-27.
9 Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):641-8.
10 Tenofovir alafenamide is not a substrate for renal organic anion transporters (OATs) and does not exhibit OAT-dependent cytotoxicity. Antivir Ther. 2014;19(7):687-92.
11 Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J Infect Dis. 2011 Jul 1;204(1):145-53.
12 Tenofovir Disoproxil Fumarate Is a New Substrate of ATP-Binding Cassette Subfamily C Member 11. Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e01725-16.
13 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
14 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
15 Mechanisms of action, pharmacology and interactions of dolutegravir. Enferm Infecc Microbiol Clin. 2015 Mar;33 Suppl 1:2-8.
16 Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity. Toxicol Sci. 2021 Nov 24;184(2):191-203. doi: 10.1093/toxsci/kfab112.
17 ClinicalTrials.gov (NCT02386098) Strategy-confirming Study of BMS-955176 to Treat HIV-1 Infected Treatment-experienced Adults
18 ClinicalTrials.gov (NCT03782142) Effect on HIV Medications on EPC Cells