Details of the Drug Combination

General Information of Drug Combination (ID: DC334QN)

• Drug Combination Name: BOCEPREVIR + Simeprevir
• Indication: Chronic Hepatitis C Infection; Status: Phase 1 [1]
• Component Drugs:
  BOCEPREVIR (DMBSHMF): Small molecular drug
  Simeprevir (DMLUA9D): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of BOCEPREVIR

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]

BOCEPREVIR Interacts with 2 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	[6]
COVID-19 3C-like protease (3CLpro)	TT1D53B	R1AB_SARS2 (3264-3569)	Inhibitor	[3]

BOCEPREVIR Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

BOCEPREVIR Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]

Indication(s) of Simeprevir

Disease Entry	ICD 11	Status	REF
Chronic HCV-1 infection	1E51.1	Approved	[4]
Renal hypoplasia	N.A.	Approved	[5]

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	[10]

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	[11]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[12]

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	[13]

References

• [1] ClinicalTrials.gov (NCT02333292) Efficacy and Safety of Therapy Against HCV Based on Direct-acting Antivirals in Real-life Conditions
• [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: 7876).
• [3] Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. 2020. April 20. doi: https://doi.org/10.1101/2020.04.20.051581
• [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: 7367).
• [5] Simeprevir FDA Label
• [6] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [7] Drug interactions and protease inhibitors used in the treatment of hepatitis C: how to manage? Eur J Clin Pharmacol. 2014 Jul;70(7):775-89.
• [8] Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin. Antimicrob Agents Chemother. 2013 Jun;57(6):2582-8.
• [9] Direct-acting antiviral agents for hepatitis C virus infection. Annu Rev Pharmacol Toxicol. 2013;53:427-49.
• [10] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [11] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [12] Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
• [13] 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.