Details of the Drug Combination

General Information of Drug Combination (ID: DCHKA22)

Drug Combination Name
Aminosalicylic Acid Pazopanib
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Aminosalicylic Acid   DMENSL5 Pazopanib   DMF57DM
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 45.79
Bliss Independence Score: 45.79
Loewe Additivity Score: 59.5
LHighest Single Agent (HSA) Score: 59.5

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 [4]
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Modulator [4]
Prostaglandin G/H synthase 2 (COX-2) TTVKILB PGH2_HUMAN Modulator [4]
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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 [5]
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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 [6]
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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 [7]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [7]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [7]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [7]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [7]
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Pazopanib Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [10]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [9]
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Pazopanib Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [11]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [12]
Myeloblastin (PRTN3) OT72MHP7 PRTN3_HUMAN Increases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [14]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [14]
HLA class I histocompatibility antigen protein P5 (HCP5) OTV0YRI8 HCP5_HUMAN Increases ADR [15]
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⏷ Show the Full List of 6 DOT(s)

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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
5 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.
6 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.
7 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.
8 Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.
9 Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35.
10 Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54.
11 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
12 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
13 Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
14 MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model. Br J Cancer. 2016 Oct 11;115(8):920-928. doi: 10.1038/bjc.2016.263. Epub 2016 Aug 25.
15 HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer. Clin Cancer Res. 2016 Mar 15;22(6):1371-7. doi: 10.1158/1078-0432.CCR-15-2044. Epub 2015 Nov 6.