Details of the Drug Combination

General Information of Drug Combination (ID: DCZ8I4I)

• Drug Combination Name: Simeprevir + Daclatasvir
• Indication: Renal Impairment; Status: Phase 2 [1]
• Component Drugs:
  Simeprevir (DMLUA9D): Small molecular drug
  Daclatasvir (DMSFK9V): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Simeprevir

Disease Entry	ICD 11	Status	REF
Chronic HCV-1 infection	1E51.1	Approved	[2]
Renal hypoplasia	N.A.	Approved	[3]

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	[6]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]

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	[8]

Indication(s) of Daclatasvir

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Approved	[4]

Daclatasvir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hepatitis C virus Non-structural 5A (HCV NS5A)	TTCJ2X8	POLG_HCV1	Inhibitor	[9]

Daclatasvir Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

Daclatasvir Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hepatitis C Virus	DC8N7ND	N. A.	Phase 1	[12]

References

• [1] ClinicalTrials.gov (NCT02397395) An Efficacy, Safety, Tolerability and Pharmacokinetics Study of 12 Weeks Treatment With Simeprevir and Daclatasvir in Participants With Chronic Hepatitis C Virus Genotype 1b or 4 Infection and Either Severe Renal Impairment or End-stage Renal Disease on Hemodialysis.
• [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: 7367).
• [3] Simeprevir FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [7] Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. Clin Pharmacokinet. 2016 Feb;55(2):197-208.
• [8] 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.
• [9] 2011 Pipeline of Bristol-Myers Squibb.
• [10] Influence of ABCB11 and HNF4 genes on daclatasvir plasma concentration: preliminary pharmacogenetic data from the Kineti-C study. J Antimicrob Chemother. 2017 Oct 1;72(10):2846-2849.
• [11] Daclatasvir: a NS5A replication complex inhibitor for hepatitis C infection. Ann Pharmacother. 2016 Jan;50(1):39-46.
• [12] ClinicalTrials.gov (NCT01628692) Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus