Details of the Drug Combination

General Information of Drug Combination (ID: DC0AG9C)

Drug Combination Name
Dexrazoxane Hepzato
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Dexrazoxane   DMD7X1O Hepzato   DM2AZPP
Small molecular drug N.A.
High-throughput Screening Result Testing Cell Line: K-562
Zero Interaction Potency (ZIP) Score: 1.26
Bliss Independence Score: 5.56
Loewe Additivity Score: 3.88
LHighest Single Agent (HSA) Score: 4.63

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 Hepzato
Disease Entry ICD 11 Status REF
Uveal Melanoma 2D0Y Phase 3 [6]

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Anaplastic large cell lymphoma DCTCEUM SR Investigative [1]
Renal cell carcinoma DCERJ1Z SN12C Investigative [1]
Adenocarcinoma DCPAZ43 HCT116 Investigative [11]
Lung adenocarcinoma DCL23F7 HOP-62 Investigative [11]
Minimally invasive lung adenocarcinoma DCPHNN9 NCI-H322M Investigative [11]
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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 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 ClinicalTrials.gov (NCT05022901) An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma. U.S.National Institutes of Health.
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 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.