Details of the Drug Combination

General Information of Drug Combination (ID: DCYCZUN)

• Drug Combination Name: Cabazitaxel + Dexrazoxane
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Dexrazoxane (DMD7X1O): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HS 578T
  Zero Interaction Potency (ZIP) Score: 8.29
  Bliss Independence Score: 7.91
  Loewe Additivity Score: 6.75
  LHighest Single Agent (HSA) Score: 9.59

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Metastatic prostate carcinoma	N.A.	Investigative	[3]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[8]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[10]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[10]

Indication(s) of Dexrazoxane

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Chemoprotection	N.A.	Approved	[5]
Inflammatory breast cancer	2C62	Approved	[6]
Respiratory tract disease	CB7Z	Investigative	[7]

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	[11]
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[12]

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	[13]

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	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCDT8JH	HT29	Investigative	[15]
Adenocarcinoma	DCEMBQU	HCT-15	Investigative	[15]
Adult acute myeloid leukemia	DCEAC0O	HL-60(TB)	Investigative	[15]
Adult T acute lymphoblastic leukemia	DCJNYGO	MOLT-4	Investigative	[15]
Anaplastic large cell lymphoma	DCFWOVY	SR	Investigative	[15]
Childhood T acute lymphoblastic leukemia	DCISSO8	CCRF-CEM	Investigative	[15]
Glioblastoma	DCB64JO	SNB-75	Investigative	[15]
High grade ovarian serous adenocarcinoma	DCQ0GGU	OVCAR-8	Investigative	[15]
Large cell lung carcinoma	DCYWEDP	NCI-H460	Investigative	[15]
Lung adenocarcinoma	DCPL8P6	MDA-MB-231	Investigative	[15]
Renal cell carcinoma	DCGYIK6	SN12C	Investigative	[15]
Carcinoma	DC1W9N0	RXF 393	Investigative	[1]

References

• [1] 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.
• [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: 6798).
• [3] Cabazitaxel 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: 7330).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Dexrazoxane FDA Label
• [7] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
• [8] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [9] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [10] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
• [11] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [13] 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.
• [14] 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.
• [15] 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.