General Information of Drug Combination (ID: DC0ISQV)

Drug Combination Name
Dacarbazine Idarubicin
Indication
Disease Entry Status REF
Glioma Investigative [1]
Component Drugs Dacarbazine   DMNPZL4 Idarubicin   DMM0XGL
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: 4.96
Bliss Independence Score: 8.15
Loewe Additivity Score: 4.13
LHighest Single Agent (HSA) Score: 9.75

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dacarbazine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [2]
Astrocytoma 2A00.0Y Approved [2]
Brain disease 8C70-8E61 Approved [2]
Central nervous system disease 8A04-8D87 Approved [2]
Glioblastoma 2A00 Approved [2]
Gliosarcoma N.A. Approved [2]
Melanoma 2C30 Approved [3]
Classic Hodgkin lymphoma N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Dacarbazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Breaker [7]
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Dacarbazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [9]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [10]
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Dacarbazine Interacts with 12 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Increases Expression [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [6]
Interferon regulatory factor 1 (IRF1) OT43DI6J IRF1_HUMAN Increases Expression [12]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Activity [13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Response To Substance [14]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Increases Response To Substance [15]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Response To Substance [16]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Response To Substance [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Response To Substance [17]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Affects Response To Substance [18]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) OTS3FVTY M3K1_HUMAN Decreases Response To Substance [17]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Decreases Response To Substance [19]
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⏷ Show the Full List of 12 DOT(s)
Indication(s) of Idarubicin
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [4]
Acute myeloid leukaemia 2A60 Approved [5]
Adult acute monocytic leukemia N.A. Approved [4]
Childhood acute megakaryoblastic leukemia N.A. Approved [4]
Leukemia N.A. Approved [4]
Idarubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [21]
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Idarubicin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [22]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [23]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [23]
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Idarubicin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [24]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [24]
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Idarubicin Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [20]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [25]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Activity [20]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [26]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Activity [20]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [27]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Decreases Activity [20]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [28]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Decreases Activity [20]
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⏷ Show the Full List of 9 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Anaplastic large cell lymphoma DCRIO9D SR Investigative [1]
Glioblastoma? DC02IWX T98G Investigative [1]
Glioma DCC3LKH SF-268 Investigative [1]
Melanoma DCYPK0H UACC-257 Investigative [1]
Pleural epithelioid mesothelioma DCBXNJ3 NCI-H226 Investigative [1]
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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 Dacarbazine FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075259.
4 Idarubicin FDA Label
5 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: 7083).
6 Dacarbazine causes transcriptional up-regulation of interleukin 8 and vascular endothelial growth factor in melanoma cells: a possible escape mechanism from chemotherapy. Mol Cancer Ther. 2003 Aug;2(8):753-63.
7 Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.
8 Study on mesenchymal stem cells mediated enzyme-prodrug gene CYP1A2 targeting anti-tumor effect. Zhonghua Xue Ye Xue Za Zhi. 2009 Oct;30(10):667-71.
9 Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1. Clin Cancer Res. 1999 Aug;5(8):2192-7.
10 Role of cytochrome P450 isoenzymes in metabolism of O(6)-benzylguanine: implications for dacarbazine activation. Clin Cancer Res. 2001 Dec;7(12):4239-44.
11 Serum bcl-2 and survivin levels in melanoma. Melanoma Res. 2004 Dec;14(6):543-6. doi: 10.1097/00008390-200412000-00017.
12 CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma. Eur J Clin Invest. 2007 Nov;37(11):887-96. doi: 10.1111/j.1365-2362.2007.01873.x.
13 Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethylnitrosourea combination therapy in patients with advanced breast cancer. Int J Cancer. 2003 Feb 20;103(5):686-92. doi: 10.1002/ijc.10849.
14 Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse xenotransplantation model. J Invest Dermatol. 2003 Jun;120(6):1081-6. doi: 10.1046/j.1523-1747.2003.12252.x.
15 Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol Cancer Res. 2009 Jun;7(6):897-906. doi: 10.1158/1541-7786.MCR-08-0519. Epub 2009 May 26.
16 Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies. Cancer Chemother Pharmacol. 2008 Mar;61(3):377-93. doi: 10.1007/s00280-007-0480-1. Epub 2007 May 23.
17 Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo. J Clin Oncol. 2004 Jun 1;22(11):2092-100. doi: 10.1200/JCO.2004.11.070. Epub 2004 May 3.
18 Clusterin regulates drug-resistance in melanoma cells. J Invest Dermatol. 2005 Jun;124(6):1300-7. doi: 10.1111/j.0022-202X.2005.23720.x.
19 Functional erythropoietin autocrine loop in melanoma. Am J Pathol. 2005 Mar;166(3):823-30. doi: 10.1016/S0002-9440(10)62303-6.
20 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
21 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
22 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
23 Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
24 In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
25 A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
26 The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
27 The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
28 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.