General Information of Drug Combination (ID: DC8X84L)

Drug Combination Name
Uracil mustard Vincristine
Indication
Disease Entry Status REF
Glioma Investigative [1]
Component Drugs Uracil mustard   DMHL7OB Vincristine   DMINOX3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SF-295
Zero Interaction Potency (ZIP) Score: 3.49
Bliss Independence Score: 4.59
Loewe Additivity Score: 1.18
LHighest Single Agent (HSA) Score: 6.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Uracil mustard
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [2]
Chronic myelogenous leukaemia 2A20.0 Approved [3]
Polycythemia vera 2A20.4 Approved [3]
Small lymphocytic lymphoma 2A82.0 Approved [3]
Uracil mustard Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [6]
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Uracil mustard Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1) OT7FBG5W NAR1_HUMAN Increases ADR [7]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases ADR [7]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases ADR [7]
Poly polymerase 1 (PARP1) OTIESHK4 PARP1_ARATH Increases ADR [7]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases ADR [7]
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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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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCNBPTD HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DC3BBSK MOLT-4 Investigative [1]
Anaplastic large cell lymphoma DCUU940 SR Investigative [1]
Childhood T acute lymphoblastic leukemia DCRYGZ5 CCRF-CEM Investigative [1]
Plasma cell myeloma DCYSEXO RPMI-8226 Investigative [1]
Colon adenocarcinoma DCIDK4A COLO 205 Investigative [15]
Adenocarcinoma DC6TTV8 DU-145 Investigative [16]
Adenocarcinoma DCO5YRY A549 Investigative [16]
Cutaneous melanoma DCL5TJG SK-MEL-5 Investigative [16]
Large cell lung carcinoma DCBX6XL NCI-H460 Investigative [16]
Minimally invasive lung adenocarcinoma DCDJ2MM NCI-H322M Investigative [16]
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⏷ Show the Full List of 11 DrugCom(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 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: 7621).
3 Uracil mustard FDA Label
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 Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
7 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
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
15 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
16 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.