Details of the Drug Combination

General Information of Drug Combination (ID: DC1X5Y5)

Drug Combination Name
VR-776 Triapine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs VR-776   DMFQWNI Triapine   DM7XZY5
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: 3.47
Bliss Independence Score: 3.47
Loewe Additivity Score: 4.36
LHighest Single Agent (HSA) Score: 4.36

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 [4]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [5]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [6]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Indication(s) of Triapine
Disease Entry ICD 11 Status REF
Nerve injury ND56.4 Phase 2 [3]
Triapine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ribonucleoside-diphosphate reductase M2 (RRM2) TTBWDI0 RIR2_HUMAN Modulator [3]
------------------------------------------------------------------------------------
Triapine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [10]
Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) OTLB2WEU PRDX3_HUMAN Increases Oxidation [9]
------------------------------------------------------------------------------------

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 PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
4 Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48.
5 Erythromycin interaction with risperidone or clomipramine in an adolescent. J Child Adolesc Psychopharmacol. 1996 Summer;6(2):133-8.
6 Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70.
7 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.
8 Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer. Pharmacogenomics. 2017 May;18(7):601-605.
9 The iron-chelating drug triapine causes pronounced mitochondrial thiol redox stress. Toxicol Lett. 2011 Mar 5;201(2):130-6. doi: 10.1016/j.toxlet.2010.12.017. Epub 2010 Dec 31.
10 Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.