Details of the Drug Combination

General Information of Drug Combination (ID: DCQBLXF)

Drug Combination Name
Tolvaptan Mefloquine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Tolvaptan   DMIWFRL Mefloquine   DMWT905
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: 7.26
Bliss Independence Score: 7.26
Loewe Additivity Score: 8.42
LHighest Single Agent (HSA) Score: 8.44

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Tolvaptan
Disease Entry ICD 11 Status REF
Autosomal dominant polycystic kidney disease GB81 Approved [2]
Hyponatraemia 5C72 Approved [3]
Heart failure BD10-BD13 Phase 3 [3]
Hypernatremia 5C71 Investigative [2]
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 [8]
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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 [9]
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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 [10]
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Tolvaptan Interacts with 7 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 [11]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Activity [11]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [11]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [12]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Activity [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [12]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Activity [11]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Mefloquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [6]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [6]
Progressive multifocal leukoencephalopathy 8A45.02 Investigative [7]
Mefloquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium 80S ribosome (Malaria 80S) TTT28H3 NOUNIPROTAC Binder [13]
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Mefloquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [14]
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Mefloquine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Tolvaptan FDA Label
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: 2226).
4 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
5 ClinicalTrials.gov (NCT04347031) An Open Randomized Study of the Effectiveness of Mefloquine for the Treatment of Patients With COVID19. U.S. National Institutes of Health.
6 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
7 Mefloquine FDA Label
8 Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
9 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.
10 Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88.
11 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.
12 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
13 An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
14 Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
15 Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.