Details of the Drug Combination

General Information of Drug Combination (ID: DCJB0ZS)

Drug Combination Name
VR-776 Pazopanib
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs VR-776   DMFQWNI 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: 36
Bliss Independence Score: 36
Loewe Additivity Score: 51.42
LHighest Single Agent (HSA) Score: 51.42

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of VR-776
Disease Entry ICD 11 Status REF
Premature ejaculation HA03.0Z Discontinued in Phase 1 [2]
VR-776 Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [3]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [4]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [5]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [6]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [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 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [11]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Expression [11]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [12]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [11]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Secretion [13]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [14]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [15]
Myeloblastin (PRTN3) OT72MHP7 PRTN3_HUMAN Increases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [16]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [16]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [14]
HLA class I histocompatibility antigen protein P5 (HCP5) OTV0YRI8 HCP5_HUMAN Increases ADR [17]
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⏷ Show the Full List of 12 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 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022099)
3 Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48.
4 Erythromycin interaction with risperidone or clomipramine in an adolescent. J Child Adolesc Psychopharmacol. 1996 Summer;6(2):133-8.
5 Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70.
6 The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64.
7 Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer. Pharmacogenomics. 2017 May;18(7):601-605.
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 Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles. Arch Toxicol. 2018 Apr;92(4):1435-1451.
12 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.
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 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.
15 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.
16 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.
17 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.