Details of the Drug Combination

General Information of Drug Combination (ID: DCW3T3D)

• Drug Combination Name: Dexrazoxane + Amonafide
• Indication: Mixed endometrioid and clear cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Dexrazoxane (DMD7X1O): Small molecular drug
  Amonafide (DMAH59S): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: IGROV1
  Zero Interaction Potency (ZIP) Score: 1.45
  Bliss Independence Score: 3.42
  Loewe Additivity Score: 6.66
  LHighest Single Agent (HSA) Score: 8.91

Molecular Interaction Atlas of This Drug Combination

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]

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]

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]

Indication(s) of Amonafide

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[6]
Ovarian cancer	2C73	Phase 3	[6]
Prostate cancer	2C82.0	Phase 3	[6]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCXWYM2	HL-60(TB)	Investigative	[11]
Adult T acute lymphoblastic leukemia	DCLU4RL	MOLT-4	Investigative	[11]
Anaplastic large cell lymphoma	DC5WJ3G	SR	Investigative	[11]
Astrocytoma	DCSOJ0S	U251	Investigative	[11]
Childhood T acute lymphoblastic leukemia	DCEIHBB	CCRF-CEM	Investigative	[11]
Chronic myelogenous leukemia	DCGOH7K	K-562	Investigative	[11]
Clear cell renal cell carcinoma	DCCYSX6	TK-10	Investigative	[11]
Glioma	DC20PZG	SF-539	Investigative	[11]
Glioma	DCWBM6B	SF-268	Investigative	[11]
Renal cell carcinoma	DCLU9JC	SN12C	Investigative	[11]
Breast adenocarcinoma	DCST2BW	MDA-MB-468	Investigative	[12]
Colon adenocarcinoma	DCF2O13	COLO 205	Investigative	[12]
Invasive ductal carcinoma	DCH8JHY	HS 578T	Investigative	[12]
Cutaneous melanoma	DCWQCOT	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC8GXLC	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC0ZC1P	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCG92IZ	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DC7N1ZO	NCI-H460	Investigative	[1]
Malignant melanoma	DCS11A4	LOX IMVI	Investigative	[1]
Pleural epithelioid mesothelioma	DCSEE3U	NCI-H226	Investigative	[1]

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] ClinicalTrials.gov (NCT00715637) Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDEStudy. 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] 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.
• [12] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.