Details of the Drug Combination

General Information of Drug Combination (ID: DCZ4WC8)

Drug Combination Name
Ribavirin-TP Tolvaptan
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Ribavirin-TP   DM09NGV Tolvaptan   DMIWFRL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 32.85
Bliss Independence Score: 32.85
Loewe Additivity Score: 46.86
LHighest Single Agent (HSA) Score: 46.86

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ribavirin-TP
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
Ribavirin-TP Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Hepatitis C virus NS3 helicase (HCV NS3) TTWXB3E POLG_HCV1 Inhibitor [2]
------------------------------------------------------------------------------------
Indication(s) of Tolvaptan
Disease Entry ICD 11 Status REF
Autosomal dominant polycystic kidney disease GB81 Approved [3]
Hyponatraemia 5C72 Approved [4]
Heart failure BD10-BD13 Phase 3 [4]
Hypernatremia 5C71 Investigative [3]
Tolvaptan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vasopressin V2 receptor (V2R) TTK8R02 V2R_HUMAN Antagonist [5]
------------------------------------------------------------------------------------
Tolvaptan 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]
------------------------------------------------------------------------------------
Tolvaptan Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
------------------------------------------------------------------------------------
Tolvaptan Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Decreases Activity [8]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Activity [8]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [8]
------------------------------------------------------------------------------------

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy. Acta Biochim Pol. 2000;47(1):173-80.
3 Tolvaptan FDA Label
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: 2226).
5 Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
6 In vitro P-glycoprotein interactions and steady-state pharmacokinetic interactions between tolvaptan and digoxin in healthy subjects. J Clin Pharmacol. 2011 May;51(5):761-9.
7 Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88.
8 Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury?. Toxicol Sci. 2016 Jan;149(1):237-50. doi: 10.1093/toxsci/kfv231. Epub 2015 Oct 26.