General Information of Drug Combination (ID: DCWJRA2)

Drug Combination Name
Linagliptin Tolvaptan
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Linagliptin   DMWFJTR 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: 22.67
Bliss Independence Score: 22.67
Loewe Additivity Score: 37.59
LHighest Single Agent (HSA) Score: 37.59

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Linagliptin
Disease Entry ICD 11 Status REF
Non-insulin dependent diabetes 5A11 Approved [2]
Type 2 diabetes 5A11 Approved [3]
Type-2 diabetes 5A11 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [5]
Linagliptin Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dipeptidyl peptidase 4 (DPP-4) TTDIGC1 DPP4_HUMAN Inhibitor [8]
HUMAN dipeptidyl peptidase 4 (DPP-4) TTF928K DPP4_HUMAN Inhibitor [9]
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Linagliptin 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]
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Indication(s) of Tolvaptan
Disease Entry ICD 11 Status REF
Autosomal dominant polycystic kidney disease GB81 Approved [6]
Hyponatraemia 5C72 Approved [7]
Heart failure BD10-BD13 Phase 3 [7]
Hypernatremia 5C71 Investigative [6]
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 [11]
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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 [12]
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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 [13]
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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 [14]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Activity [14]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [14]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [15]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Activity [14]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [15]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Activity [14]
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⏷ Show the Full List of 7 DOT(s)

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 Linagliptin FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 208026
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: 6318).
5 ClinicalTrials.gov (NCT04371978) Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19. U.S. National Institutes of Health.
6 Tolvaptan FDA Label
7 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).
8 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
9 DPP4 inhibition: preventing SARS-CoV-2 infection and/or progression of COVID-19 Diabetes Metab Res Rev. 2020 Apr 26.
10 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
11 Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
12 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.
13 Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88.
14 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.
15 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.