General Information of Drug Combination (ID: DC0PERD)

Drug Combination Name
MK-1775 Vincristine
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs MK-1775   DM3WDZ5 Vincristine   DMINOX3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 11.277
Bliss Independence Score: 9.231
Loewe Additivity Score: 0.422
LHighest Single Agent (HSA) Score: 3.39

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-1775
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
MK-1775 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Wee1-like protein kinase (WEE1) TTJFOAL WEE1_HUMAN Inhibitor [7]
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MK-1775 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [6]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [6]
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Indication(s) of Vincristine
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [4]
Adult kidney Wilms tumor N.A. Approved [5]
Beckwith-Wiedemann syndrome N.A. Approved [5]
Burkitt lymphoma N.A. Approved [5]
Central nervous system neoplasm N.A. Approved [5]
Childhood acute lymphoblastic leukemia N.A. Approved [5]
Childhood kidney Wilms tumor N.A. Approved [5]
Hamartoma N.A. Approved [5]
Kidney neoplasm N.A. Approved [5]
Leukemia N.A. Approved [5]
MALT lymphoma N.A. Approved [5]
Nodal marginal zone lymphoma 2A85.0 Approved [5]
Plasma cell myeloma 2A83.1 Approved [5]
Primitive neuroectodermal tumor N.A. Approved [5]
Splenic marginal zone lymphoma N.A. Approved [5]
Testicular lymphoma N.A. Approved [5]
Wilms tumor N.A. Approved [5]
Classic Hodgkin lymphoma N.A. Investigative [5]
Follicular lymphoma 2A80 Investigative [5]
Neuroblastoma 2D11.2 Investigative [5]
Vincristine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tubulin beta (TUBB) TTYFKSZ NOUNIPROTAC Modulator [8]
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Vincristine Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [9]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [10]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [12]
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Vincristine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [13]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [14]
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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 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: 7702).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 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: 6785).
5 Vincristine FDA Label
6 Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
7 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol. 2008 Sep 4;591(1-3):128-31.
10 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
11 L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines. Toxicol Lett. 2010 Feb 15;192(3):408-18.
12 Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
13 Association of CYP3A5 expression and vincristine neurotoxicity in pediatric malignancies in Turkish population. J Pediatr Hematol Oncol. 2017 Aug;39(6):458-462.
14 Drug Interactions Flockhart Table