Details of the Drug Combination

General Information of Drug Combination (ID: DCVSPRY)

Drug Combination Name
Aminosalicylic Acid Tolvaptan
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Aminosalicylic Acid   DMENSL5 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: 24.02
Bliss Independence Score: 24.02
Loewe Additivity Score: 39.19
LHighest Single Agent (HSA) Score: 39.19

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Aminosalicylic Acid
Disease Entry ICD 11 Status REF
Crohn disease DD70 Approved [2]
Inflammatory bowel disease DD72 Approved [3]
Pulmonary and extrapulmonary tuberculosis 1B10.Z Approved [3]
Pulmonary tuberculosis 1B10.Z Approved [2]
Ulcerative colitis DD71 Approved [2]
Aminosalicylic Acid Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dihydrofolate reductase (DHFR) TTYZVDJ DYR_HUMAN Modulator [6]
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Modulator [6]
Prostaglandin G/H synthase 2 (COX-2) TTVKILB PGH2_HUMAN Modulator [6]
------------------------------------------------------------------------------------
Aminosalicylic Acid Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Sodium-coupled neutral amino acid transporter 3 (SLC38A3) DTKWJH3 S38A3_HUMAN Substrate [7]
------------------------------------------------------------------------------------
Aminosalicylic Acid Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
N-acetyltransferase 2 (NAT2) DER7TA0 ARY2_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Aminosalicylic Acid Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [9]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [9]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [9]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [9]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [9]
------------------------------------------------------------------------------------
Indication(s) of Tolvaptan
Disease Entry ICD 11 Status REF
Autosomal dominant polycystic kidney disease GB81 Approved [4]
Hyponatraemia 5C72 Approved [5]
Heart failure BD10-BD13 Phase 3 [5]
Hypernatremia 5C71 Investigative [4]
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 [10]
------------------------------------------------------------------------------------
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 [11]
------------------------------------------------------------------------------------
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 [12]
------------------------------------------------------------------------------------
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 [13]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Decreases Activity [13]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [13]
------------------------------------------------------------------------------------

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Aminosalicylic acid FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Tolvaptan FDA Label
5 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).
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Identification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2. Biochem J. 2000 May 15;348 Pt 1:159-66.
8 Importance of the evaluation of N-acetyltransferase enzyme activity prior to 5-aminosalicylic acid medication for ulcerative colitis. Inflamm Bowel Dis. 2016 Aug;22(8):1793-802.
9 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
10 Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009 May 1;419(3):577-84.
11 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.
12 Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88.
13 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.