Details of the Drug Combination

General Information of Drug Combination (ID: DC4YBP1)

• Drug Combination Name: Dolutegravir + Simeprevir
• Indication: HIV; Status: Phase 1 [1]
• Component Drugs:
  Dolutegravir (DMCZGRE): Small molecular drug
  Simeprevir (DMLUA9D): 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 Simeprevir

Disease Entry	ICD 11	Status	REF
Chronic HCV-1 infection	1E51.1	Approved	[3]
Renal hypoplasia	N.A.	Approved	[4]

Simeprevir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A)	TTHC7JD	POLG_HCV1	Modulator	[5]

Simeprevir 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]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[10]

Simeprevir Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]

References

• [1] ClinicalTrials.gov (NCT02404805) Drug Interaction Potential Between Dolutegravir and Simeprevir in HIV/HCV Seronegative Volunteers
• [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] 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: 7367).
• [4] Simeprevir FDA Label
• [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] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [10] Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
• [11] Hepatitis C virus direct-acting antiviral drug interactions and use in renal and hepatic impairment. Top Antivir Med. 2015 May-Jun;23(2):92-6.