General Information of Drug Combination (ID: DCUUJMY)

Drug Combination Name
Thioguanine Vincristine
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Thioguanine   DM7NKEV Vincristine   DMINOX3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: OVCAR3
Zero Interaction Potency (ZIP) Score: 9.46
Bliss Independence Score: 13.62
Loewe Additivity Score: 5.21
LHighest Single Agent (HSA) Score: 14.72

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Thioguanine
Disease Entry ICD 11 Status REF
Acute lymphocytic leukaemia 2B33.3 Approved [2]
Acute myelogenous leukaemia 2A41 Approved [3]
Acute myeloid leukaemia 2A60 Approved [4]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [5]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [5]
Thioguanine Interacts with 3 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 [5]
Inosine-5'-monophosphate dehydrogenase (IMPDH) TTCAQMW NOUNIPROTAC Intercalator [8]
SARS-CoV papain-like proteinase (PL-PRO) TTRGHB2 R1AB_CVHSA (819-2740) Inhibitor [5]
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Thioguanine Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [10]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3) DT4YL5R S28A3_HUMAN Substrate [11]
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Thioguanine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [12]
Hypoxanthine phosphoribosyltransferase (HPRT1) DEVXTP5 HPRT_HUMAN Metabolism [13]
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Thioguanine Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Increases ADR [14]
Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) OTOEEEXG HPRT_HUMAN Decreases Response To Substance [15]
Thiopurine S-methyltransferase (TPMT) OTFOX70W TPMT_HUMAN Increases ADR [16]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) OTPG0K7E IMDH2_HUMAN Increases Expression [17]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [18]
Dystrophin (DMD) OTD21T5J DMD_HUMAN Increases Splicing [19]
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Decreases Activity [20]
DNA mismatch repair protein Msh2 (MSH2) OT10H1AB MSH2_HUMAN Increases Response To Substance [21]
ATP-binding cassette sub-family C member 5 (ABCC5) OT34G4US MRP5_HUMAN Decreases Response To Substance [22]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Response To Substance [18]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [23]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Vincristine
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [6]
Adult kidney Wilms tumor N.A. Approved [7]
Beckwith-Wiedemann syndrome N.A. Approved [7]
Burkitt lymphoma N.A. Approved [7]
Central nervous system neoplasm N.A. Approved [7]
Childhood acute lymphoblastic leukemia N.A. Approved [7]
Childhood kidney Wilms tumor N.A. Approved [7]
Hamartoma N.A. Approved [7]
Kidney neoplasm N.A. Approved [7]
Leukemia N.A. Approved [7]
MALT lymphoma N.A. Approved [7]
Nodal marginal zone lymphoma 2A85.0 Approved [7]
Plasma cell myeloma 2A83.1 Approved [7]
Primitive neuroectodermal tumor N.A. Approved [7]
Splenic marginal zone lymphoma N.A. Approved [7]
Testicular lymphoma N.A. Approved [7]
Wilms tumor N.A. Approved [7]
Classic Hodgkin lymphoma N.A. Investigative [7]
Follicular lymphoma 2A80 Investigative [7]
Neuroblastoma 2D11.2 Investigative [7]
Vincristine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tubulin beta (TUBB) TTYFKSZ NOUNIPROTAC Modulator [24]
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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 [25]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [26]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [27]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [28]
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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 [29]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [29]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [30]
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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 DC6GEYF HL-60(TB) Investigative [31]
Adult T acute lymphoblastic leukemia DCVBM2B MOLT-4 Investigative [31]
Anaplastic large cell lymphoma DCUMSR6 SR Investigative [31]
Childhood T acute lymphoblastic leukemia DCV5SNH CCRF-CEM Investigative [31]
Clear cell renal cell carcinoma DC5QG4P 786-0 Investigative [31]
Clear cell renal cell carcinoma DC784KE A498 Investigative [31]
Clear cell renal cell carcinoma DCQ2JU8 CAKI-1 Investigative [31]
Glioma DCGHNZD SF-295 Investigative [31]
Papillary renal cell carcinoma DCAEDRB ACHN Investigative [31]
Renal cell carcinoma DC6LHLZ SN12C Investigative [31]
Adenocarcinoma DC2BBEM DU-145 Investigative [1]
Adenocarcinoma DC2XM9J A549 Investigative [1]
Adenocarcinoma DCL81ZA HCT-15 Investigative [1]
Amelanotic melanoma DCJJ0K2 M14 Investigative [1]
Cutaneous melanoma DCDZ06U SK-MEL-5 Investigative [1]
High grade ovarian serous adenocarcinoma DCDKOS1 NCI\\/ADR-RES Investigative [1]
Large cell lung carcinoma DCZJBJ8 NCI-H460 Investigative [1]
Malignant melanoma DCE9Z4Y LOX IMVI Investigative [1]
Minimally invasive lung adenocarcinoma DCMSZFP NCI-H322M Investigative [1]
Mixed endometrioid and clear cell carcinoma DCBJ9XD IGROV1 Investigative [1]
Non-small cell lung carcinoma DC8PHJA HOP-92 Investigative [1]
Ovarian serous cystadenocarcinoma DCSJBCD SK-OV-3 Investigative [1]
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⏷ Show the Full List of 22 DrugCom(s)

References

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2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Thioguanine 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: 6845).
5 Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015 Mar;115:9-16.
6 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).
7 Vincristine FDA Label
8 Immune effector cells produce lethal DNA damage in cells treated with a thiopurine. Cancer Res. 2009 Mar 15;69(6):2393-9.
9 ABC transporters and their role in nucleoside and nucleotide drug resistance. Biochem Pharmacol. 2012 Apr 15;83(8):1073-83.
10 Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57.
11 Involvement of the concentrative nucleoside transporter 3 and equilibrative nucleoside transporter 2 in the resistance of T-lymphoblastic cell lines to thiopurines. Biochem Biophys Res Commun. 2006 Apr 28;343(1):208-15.
12 Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in clinical practice in patients with inflammatory bowel diseases. Acta Gastroenterol Belg. 2010 Jul-Sep;73(3):331-5.
13 Qualitative and quantitative difference in mutation induction between carbon- and neon-ion beams in normal human cells. Biol Sci Space. 2003 Dec;17(4):302-6.
14 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.
15 CRISPR/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection. J Biol Chem. 2017 Jun 23;292(25):10664-10671. doi: 10.1074/jbc.M117.782425. Epub 2017 Apr 26.
16 Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011 Mar;89(3):387-91. doi: 10.1038/clpt.2010.320. Epub 2011 Jan 26.
17 Petit E, Langouet S, Akhdar H, Nicolas-Nicolaz C, Guillouzo A, Morel F. Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes. Toxicol In Vitro. 2008;22(3):632-642. [PMID: 18222062]
18 Important role of caspase-8 for chemosensitivity of ALL cells. Clin Cancer Res. 2011 Dec 15;17(24):7605-13. doi: 10.1158/1078-0432.CCR-11-0513. Epub 2011 Oct 18.
19 The effect of 6-thioguanine on alternative splicing and antisense-mediated exon skipping treatment for duchenne muscular dystrophy. PLoS Curr. 2012 Dec 12;4:ecurrents.md.597d700f92eaa70de261ea0d91821377. doi: 10.1371/currents.md.597d700f92eaa70de261ea0d91821377.
20 The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther. 2006 Oct;80(4):375-83. doi: 10.1016/j.clpt.2006.07.002.
21 The effect of Msh2 knockdown on methylating agent induced toxicity in DNA glycosylase deficient cells. Toxicology. 2010 Jan 31;268(1-2):111-7. doi: 10.1016/j.tox.2009.12.008. Epub 2009 Dec 16.
22 The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol Cancer Ther. 2005 May;4(5):855-63.
23 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
24 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
25 Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol. 2008 Sep 4;591(1-3):128-31.
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27 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.
28 Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
29 Association of CYP3A5 expression and vincristine neurotoxicity in pediatric malignancies in Turkish population. J Pediatr Hematol Oncol. 2017 Aug;39(6):458-462.
30 Drug Interactions Flockhart Table
31 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.