Details of the Drug Combination

General Information of Drug Combination (ID: DCH34NK)

Drug Combination Name
Pazopanib Novobiocin
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pazopanib   DMF57DM Novobiocin   DMRFWGK
N.A. 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: 56.1
Bliss Independence Score: 56.1
Loewe Additivity Score: 69.12
LHighest Single Agent (HSA) Score: 69.12

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [4]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [4]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [5]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [4]
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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 [6]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [7]
Myeloblastin (PRTN3) OT72MHP7 PRTN3_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [9]
HLA class I histocompatibility antigen protein P5 (HCP5) OTV0YRI8 HCP5_HUMAN Increases ADR [10]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Novobiocin
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [2]
Novobiocin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Inhibitor [11]
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Novobiocin Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Decreases Expression [12]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Activity [13]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
3 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.
4 Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35.
5 Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54.
6 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.
7 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.
8 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.
9 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.
10 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.
11 Transcriptional responses of Bacillus subtillis and thuringiensis to antibiotics and anti-tumour drugs. Int J Mol Med. 2009 Jan;23(1):33-9.
12 Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage. Biochim Biophys Acta. 2002 Jan 30;1542(1-3):32-40. doi: 10.1016/s0167-4889(01)00163-x.
13 Interactions between Oroxylin A with the solute carrier transporters and ATP-binding cassette transporters: Drug transporters profile for this flavonoid. Chem Biol Interact. 2020 Jun 1;324:109097. doi: 10.1016/j.cbi.2020.109097. Epub 2020 Apr 16.