Details of the Drug Combination

General Information of Drug Combination (ID: DCAWUAP)

• Drug Combination Name: Dolutegravir + Tenofovir alafenamide
• Indication: Amyotrophic Lateral Sclerosis; Status: Phase 1 [1]
• Component Drugs:
  Dolutegravir (DMCZGRE): Small molecular drug
  Tenofovir alafenamide (DMTQF4A): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dolutegravir

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

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	[4]

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	[5]

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	[6]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[6]

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	[7]
T-box transcription factor TBX6 (TBX6)	OTW1Q8RM	TBX6_HUMAN	Increases Expression	[7]
Homeobox protein Hox-B1 (HOXB1)	OTGC0EKI	HXB1_HUMAN	Increases Expression	[7]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Increases Expression	[7]
Homeobox protein MIXL1 (MIXL1)	OT584VOQ	MIXL1_HUMAN	Increases Expression	[7]

Indication(s) of Tenofovir alafenamide

Disease Entry	ICD 11	Status	REF
HIV infectious disease	N.A.	Approved	[3]

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	[8]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]

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	[9]
Cathepsin A (CTSA)	DE14JZK	PPGB_HUMAN	Metabolism	[10]

References

• [1] ClinicalTrials.gov (NCT02437110) HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
• [2] 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).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [5] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [6] Mechanisms of action, pharmacology and interactions of dolutegravir. Enferm Infecc Microbiol Clin. 2015 Mar;33 Suppl 1:2-8.
• [7] 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.
• [8] Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472.
• [9] FDA label of Bictegravir, emtricitabine, and tenofovir alafenamide. The 2020 official website of the U.S. Food and Drug Administration.
• [10] Bictegravir/Emtricitabine/Tenofovir Alafenamide: a review in HIV-1 infection. Drugs. 2018 Nov;78(17):1817-1828.