Details of the Drug Combination

General Information of Drug Combination (ID: DC0YMH3)

Drug Combination Name
Dexrazoxane SCH 727965
Indication
Disease Entry Status REF
Amelanotic melanoma Investigative [1]
Component Drugs Dexrazoxane   DMD7X1O SCH 727965   DMCJLD1
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: M14
Zero Interaction Potency (ZIP) Score: 0.49
Bliss Independence Score: 2.32
Loewe Additivity Score: 0.76
LHighest Single Agent (HSA) Score: 0.34

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dexrazoxane
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Chemoprotection N.A. Approved [3]
Inflammatory breast cancer 2C62 Approved [4]
Respiratory tract disease CB7Z Investigative [5]
Dexrazoxane Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II beta (TOP2B) TT4NVEM TOP2B_HUMAN Inhibitor [7]
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [8]
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Dexrazoxane Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Dihydropyrimidinase-related protein 1 (DRP1) DE0EUXB DPYL1_HUMAN Metabolism [9]
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Dexrazoxane Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Activity [10]
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Indication(s) of SCH 727965
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Discontinued in Phase 3 [6]
SCH 727965 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [11]
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [11]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [11]
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SCH 727965 Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [12]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [12]
Breast cancer type 1 susceptibility protein (BRCA1) OT5BN6VH BRCA1_HUMAN Decreases Expression [13]
Breast cancer type 2 susceptibility protein (BRCA2) OTF1XSV1 BRCA2_HUMAN Decreases Expression [13]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [13]
Fanconi anemia group D2 protein (FANCD2) OTVEB5LF FACD2_HUMAN Decreases Expression [13]
Cyclin-dependent kinase 12 (CDK12) OTZUDGNU CDK12_HUMAN Decreases Activity [13]
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⏷ Show the Full List of 7 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DC97S69 MOLT-4 Investigative [14]
Anaplastic large cell lymphoma DC4TJDC SR Investigative [14]
Adenocarcinoma DC92L20 A549 Investigative [1]
Adenocarcinoma DCZGZUU HCT116 Investigative [1]
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References

1 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.
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: 7330).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Dexrazoxane FDA Label
5 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
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: 7379).
7 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Metabolism of the cardioprotective drug dexrazoxane and one of its metabolites by isolated rat myocytes, hepatocytes, and blood. Drug Metab Dispos. 2005 Jun;33(6):719-25.
10 Investigation of novel dexrazoxane analogue JR-311 shows significant cardioprotective effects through topoisomerase IIbeta but not its iron chelating metabolite. Toxicology. 2017 Dec 1;392:1-10. doi: 10.1016/j.tox.2017.09.012. Epub 2017 Sep 21.
11 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
12 Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010 Aug;9(8):2344-53. doi: 10.1158/1535-7163.MCT-10-0324. Epub 2010 Jul 27.
13 CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077.
14 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.