Details of the Drug Combination

General Information of Drug Combination (ID: DCK7IB0)

• Drug Combination Name: Anastrozole + FORMESTANE
• Indication: Renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  FORMESTANE (DMWIDJK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SN12C
  Zero Interaction Potency (ZIP) Score: 2.93
  Bliss Independence Score: 0.12
  Loewe Additivity Score: 0.93
  LHighest Single Agent (HSA) Score: 1.36

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	[5]

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	[6]

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	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[7]

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	[8]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[9]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[10]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Decreases Activity	[11]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[12]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[13]

Indication(s) of FORMESTANE

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Withdrawn from market	[4]

FORMESTANE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[14]

FORMESTANE Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[8]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[15]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Decreases Activity	[16]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[17]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[17]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCNIT92	SW-620	Investigative	[1]
Adenocarcinoma	DCGAMLA	HCT-15	Investigative	[1]
Adenocarcinoma	DCMGUX2	HT29	Investigative	[1]
Adult acute myeloid leukemia	DC7KDPM	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DC3B40U	MOLT-4	Investigative	[1]
Amelanotic melanoma	DCGINAD	M14	Investigative	[1]
Amelanotic melanoma	DC4AAGR	MDA-MB-435	Investigative	[1]
Clear cell renal cell carcinoma	DC41T82	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DC8ZQ0N	CAKI-1	Investigative	[1]
Lung adenocarcinoma	DCL4RZY	EKVX	Investigative	[1]
Malignant melanoma	DCIUPEX	UACC62	Investigative	[1]
Melanoma	DCC1U82	UACC-257	Investigative	[1]
Melanoma	DC6I9H3	MALME-3M	Investigative	[1]
Prostate carcinoma	DC4HGYB	PC-3	Investigative	[1]
Invasive ductal carcinoma	DCWW216	T-47D	Investigative	[18]

References

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• [3] Anastrozole FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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• [13] Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists. J Clin Oncol. 2005 Apr 10;23(11):2477-92. doi: 10.1200/JCO.2005.07.559. Epub 2005 Mar 14.
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• [16] Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7.
• [17] Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays. Toxicol Lett. 2018 Aug;292:39-45. doi: 10.1016/j.toxlet.2018.04.026. Epub 2018 Apr 24.
• [18] 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.