General Information of Drug Combination (ID: DCSA5T9)

Drug Combination Name
Vincristine Mercaptopurine
Indication
Disease Entry Status REF
Glioma Investigative [1]
Component Drugs Vincristine   DMINOX3 Mercaptopurine   DMTM2IK
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: 1.53
Bliss Independence Score: 12.62
Loewe Additivity Score: 2.06
LHighest Single Agent (HSA) Score: 2.9

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Vincristine
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [2]
Adult kidney Wilms tumor N.A. Approved [3]
Beckwith-Wiedemann syndrome N.A. Approved [3]
Burkitt lymphoma N.A. Approved [3]
Central nervous system neoplasm N.A. Approved [3]
Childhood acute lymphoblastic leukemia N.A. Approved [3]
Childhood kidney Wilms tumor N.A. Approved [3]
Hamartoma N.A. Approved [3]
Kidney neoplasm N.A. Approved [3]
Leukemia N.A. Approved [3]
MALT lymphoma N.A. Approved [3]
Nodal marginal zone lymphoma 2A85.0 Approved [3]
Plasma cell myeloma 2A83.1 Approved [3]
Primitive neuroectodermal tumor N.A. Approved [3]
Splenic marginal zone lymphoma N.A. Approved [3]
Testicular lymphoma N.A. Approved [3]
Wilms tumor N.A. Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [3]
Follicular lymphoma 2A80 Investigative [3]
Neuroblastoma 2D11.2 Investigative [3]
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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Indication(s) of Mercaptopurine
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [4]
Acute lymphocytic leukaemia 2B33.3 Approved [5]
Crohn disease DD70 Phase 4 [6]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [7]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [7]
Mercaptopurine Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MERS-CoV papain-like proteinase (PL-PRO) TTYJOLE R1AB_CVEMC (854-2740) Inhibitor [7]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) TTL7C8Q IMDH1_HUMAN Inhibitor [17]
SARS-CoV papain-like proteinase (PL-PRO) TTRGHB2 R1AB_CVHSA (819-2740) Inhibitor [7]
Amidophosphoribosyltransferase (PPAT) TTZFTY4 PUR1_HUMAN Breaker [18]
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Mercaptopurine Interacts with 9 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [19]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [20]
Multidrug resistance-associated protein 5 (ABCC5) DTYVM24 MRP5_HUMAN Substrate [21]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [22]
Concentrative nucleoside transporter 2 (SLC28A2) DT82KPY S28A2_HUMAN Substrate [23]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3) DT4YL5R S28A3_HUMAN Substrate [24]
Equilibrative nucleoside transporter 1 (SLC29A1) DTXD1TQ S29A1_HUMAN Substrate [23]
Equilibrative nucleoside transporter 2 (SLC29A2) DTW78DQ S29A2_HUMAN Substrate [23]
Equilibrative nucleobase transporter 1 (SLC43A3) DTGBPR5 S43A3_HUMAN Substrate [25]
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⏷ Show the Full List of 9 DTP(s)
Mercaptopurine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [26]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [26]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [27]
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Mercaptopurine Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Affects Response To Substance [28]
Nuclear receptor subfamily 4 group A member 3 (NR4A3) OTPBE9R1 NR4A3_HUMAN Increases ADR [29]
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Decreases Metabolism [30]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [31]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Increases Expression [31]
Glutathione peroxidase 2 (GPX2) OTXI2NTI GPX2_HUMAN Increases Expression [31]
Glutathione peroxidase 3 (GPX3) OT6PK94R GPX3_HUMAN Increases Expression [31]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Increases Expression [31]
Glutathione synthetase (GSS) OTVSBEIW GSHB_HUMAN Increases Expression [31]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) OTBPMIMW G3P_HUMAN Affects Localization [32]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [33]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1) OT4Y9NQI MP2K1_HUMAN Decreases Phosphorylation [15]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Affects Localization [15]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [15]
Molybdenum cofactor sulfurase (MOCOS) OT0TL3Q5 MOCOS_HUMAN Decreases Oxidation [34]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Affects Response To Substance [35]
Major vault protein (MVP) OTJGHJRB MVP_HUMAN Decreases Response To Substance [36]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1) OTRGGIFP DRB1_HUMAN Affects Response To Substance [35]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Affects Response To Substance [16]
Nucleotide triphosphate diphosphatase NUDT15 (NUDT15) OTX8SZOT NUD15_HUMAN Increases Response To Substance [37]
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⏷ Show the Full List of 20 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCYJZJZ 786-0 Investigative [1]
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References

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3 Vincristine 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: 7226).
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 ClinicalTrials.gov (NCT00846703) The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia. U.S. National Institutes of Health.
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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
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20 Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
21 Overexpression of MRP4 (ABCC4) and MRP5 (ABCC5) confer resistance to the nucleoside analogs cytarabine and troxacitabine, but not gemcitabine. Springerplus. 2014 Dec 13;3:732.
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25 Characterization of 6-Mercaptopurine Transport by the SLC43A3-Encoded Nucleobase Transporter. Mol Pharmacol. 2019 Jun;95(6):584-596.
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33 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
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36 Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett. 2009 Jun 28;279(1):74-83. doi: 10.1016/j.canlet.2009.01.027. Epub 2009 Feb 18.
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