Details of the Drug Combination

General Information of Drug Combination (ID: DCXCEKO)

• Drug Combination Name: Anastrozole + Dexrazoxane
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  Dexrazoxane (DMD7X1O): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HCT116
  Zero Interaction Potency (ZIP) Score: 3.38
  Bliss Independence Score: 4.28
  Loewe Additivity Score: 3.66
  LHighest Single Agent (HSA) Score: 4.99

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Anastrozole

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Estrogen-receptor positive breast cancer	N.A.	Approved	[3]
Obesity	5B81	Approved	[3]

Anastrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[8]

Anastrozole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Putative sodium-coupled neutral amino acid transporter 7 (SLC38A7)	DT2EGUN	S38A7_HUMAN	Substrate	[9]

Anastrozole Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[10]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[10]

Anastrozole Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[11]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[12]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[13]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Decreases Activity	[14]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[15]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[16]

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	[17]
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[18]

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	[19]

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	[20]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCAZ41K	OVCAR3	Investigative	[1]
Adenocarcinoma	DC4NLZD	SW-620	Investigative	[1]
Adenocarcinoma	DCBEBJD	HT29	Investigative	[1]
Adult acute myeloid leukemia	DCXFZFC	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCZ1RMC	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DCUOIUK	SR	Investigative	[1]
Clear cell renal cell carcinoma	DCPBQJG	A498	Investigative	[1]
Cutaneous melanoma	DCXDTIC	SK-MEL-5	Investigative	[1]
Glioma	DC6LMTT	SF-539	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC3IMEK	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCK5U6P	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCN90UU	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DCOOP9A	NCI-H460	Investigative	[1]
Malignant melanoma	DCB2E45	LOX IMVI	Investigative	[1]
Melanoma	DC76G7Q	MALME-3M	Investigative	[1]
Papillary renal cell carcinoma	DCFPXEO	ACHN	Investigative	[1]
Renal cell carcinoma	DC3U4VG	SN12C	Investigative	[1]
Renal cell carcinoma	DCNFXXR	UO-31	Investigative	[1]
Colon adenocarcinoma	DCYMOIL	COLO 205	Investigative	[21]
Colon carcinoma	DCF720F	KM12	Investigative	[21]
Invasive ductal carcinoma	DCNPD7L	HS 578T	Investigative	[21]

References

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• [3] Anastrozole FDA Label
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• [20] 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.
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