Details of the Drug Combination

General Information of Drug Combination (ID: DCFT2DA)

• Drug Combination Name: Dolutegravir + Darunavir
• Indication: HIV-infection/Aids; Status: Phase 4 [1]
• Component Drugs:
  Dolutegravir (DMCZGRE): Small molecular drug
  Darunavir (DMN3GCH): Small molecular drug

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	[5]

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	[6]

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	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]

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

Indication(s) of Darunavir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]
Human immunodeficiency virus-1 infection	1C62	Phase 3	[4]

Darunavir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Protease (HIV PR)	TT5FNQT	POL_HV1B1	Modulator	[9]

Darunavir Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[12]

Darunavir Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
HIV Infections	DCNCFTE	N. A.	Phase 4	[14]
HIV-Infection	DCGBRQN	N. A.	Phase 3	[15]

References

• [1] ClinicalTrials.gov (NCT04183738) Inflammation and Co-Infections in DEFT
• [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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [7] Mechanisms of action, pharmacology and interactions of dolutegravir. Enferm Infecc Microbiol Clin. 2015 Mar;33 Suppl 1:2-8.
• [8] 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.
• [9] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [10] Impact of drug transporters on cellular resistance towards saquinavir and darunavir. J Antimicrob Chemother. 2010 Nov;65(11):2319-28.
• [11] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [12] P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines. Biol Pharm Bull. 2009 Sep;32(9):1588-93.
• [13] Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41.
• [14] ClinicalTrials.gov (NCT03017872) Dolutegravir and Darunavir Evaluation in Adults Failing Therapy
• [15] ClinicalTrials.gov (NCT02486133) Dual Therapy With Boosted Darunavir + Dolutegravir