Details of the Drug Combination

General Information of Drug Combination (ID: DC8EIXR)

Drug Combination Name
Oxyphenbutazone Tolvaptan
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Oxyphenbutazone   DMPZS7U 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: 0.28
Bliss Independence Score: 0.28
Loewe Additivity Score: 7.36
LHighest Single Agent (HSA) Score: 7.36

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Oxyphenbutazone
Disease Entry ICD 11 Status REF
Arthritis FA20 Approved [2]
Oxyphenbutazone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serum albumin (ALB) TTFNGC9 ALBU_HUMAN Modulator [5]
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Oxyphenbutazone Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Increases Activity [6]
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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 [7]
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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 [8]
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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 [9]
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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 [10]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Activity [10]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [10]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [11]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Decreases Activity [10]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [11]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Activity [10]
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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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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 Effect of albumin conformation on binding of phenylbutazone and oxyphenbutazone to human serum albumin. J Pharm Sci. 1982 Feb;71(2):241-4.
6 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
7 Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
8 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.
9 Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88.
10 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.
11 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.