General Information of Drug Combination (ID: DCQZSDF)

Drug Combination Name
Thioguanine Chlorambucil
Indication
Disease Entry Status REF
Glioma Investigative [1]
Component Drugs Thioguanine   DM7NKEV Chlorambucil   DMRKE63
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: 2.75
Bliss Independence Score: 7.01
Loewe Additivity Score: 3.84
LHighest Single Agent (HSA) Score: 8.01

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 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Decreases Activity [14]
ATP-binding cassette sub-family C member 5 (ABCC5) OT34G4US MRP5_HUMAN Decreases Response To Substance [15]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [16]
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Indication(s) of Chlorambucil
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [6]
Small lymphocytic lymphoma 2A82.0 Approved [7]
Classic Hodgkin lymphoma N.A. Investigative [7]
Follicular lymphoma 2A80 Investigative [7]
Chlorambucil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA replication (DNA repli) TTABD5E NOUNIPROTAC Intercalator [17]
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Chlorambucil Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [18]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [19]
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Chlorambucil Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [20]
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Chlorambucil Interacts with 21 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [21]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Decreases Expression [22]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Expression [22]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [22]
F-box only protein 30 (FBXO30) OTD1P6LA FBX30_HUMAN Decreases Expression [22]
Histone chaperone ASF1A (ASF1A) OT4S44GP ASF1A_HUMAN Decreases Expression [22]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Affects Expression [23]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [24]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Affects Expression [25]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [26]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [27]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1) OT7OG7Y2 DPA1_HUMAN Affects Expression [28]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [29]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Increases Expression [24]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [30]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [27]
kinase isozyme 4, mitochondrial (PDK4) OTCMHMBZ PDK4_HUMAN Affects Expression [31]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [25]
Fanconi anemia group G protein (FANCG) OT7MC8TZ FANCG_HUMAN Increases Response To Substance [32]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [16]
Fanconi anemia group C protein (FANCC) OTTIDM3P FANCC_HUMAN Increases Response To Substance [32]
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⏷ Show the Full List of 21 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCRQCVA HL-60(TB) Investigative [1]
Anaplastic large cell lymphoma DCVXYEO SR Investigative [1]
Childhood T acute lymphoblastic leukemia DCB2BC4 CCRF-CEM Investigative [1]
Glioblastoma DC0I6H1 SNB-75 Investigative [1]
Breast adenocarcinoma DCHUDB6 MDA-MB-468 Investigative [33]
Colon adenocarcinoma DCKEV10 COLO 205 Investigative [33]
Adenocarcinoma DCLTOFJ HCT116 Investigative [34]
Minimally invasive lung adenocarcinoma DCECL80 NCI-H322M Investigative [34]
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⏷ Show the Full List of 8 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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: 7143).
7 Chlorambucil 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 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.
15 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.
16 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
17 Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A. Mol Cancer Ther. 2009 Jun;8(6):1714-23.
18 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.
19 Transporters and renal drug elimination. Annu Rev Pharmacol Toxicol. 2004;44:137-66.
20 The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
21 Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
22 Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
23 Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
24 Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
25 Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70. J Cell Physiol. 2007 Oct;213(1):229-36. doi: 10.1002/jcp.21116.
26 Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells. Blood. 1996 Sep 15;88(6):2172-82.
27 A two-hit mechanism for pre-mitotic arrest of cancer cell proliferation by a polyamide-alkylator conjugate. Cell Cycle. 2006 Jul;5(14):1537-48. doi: 10.4161/cc.5.14.2913. Epub 2006 Jul 17.
28 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
29 Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
30 Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an androgen receptor ligand. Chem Biol. 2005 Jul;12(7):779-87. doi: 10.1016/j.chembiol.2005.05.009.
31 The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
32 In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005 Oct 15;11(20):7508-15. doi: 10.1158/1078-0432.CCR-05-1048.
33 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
34 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976