Details of the Drug Combination

General Information of Drug Combination (ID: DCRTG1K)

• Drug Combination Name: Estramustine + FORMESTANE
• Indication: Carcinoma; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  FORMESTANE (DMWIDJK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MCF7
  Zero Interaction Potency (ZIP) Score: 2.35
  Bliss Independence Score: 8.12
  Loewe Additivity Score: 1.95
  LHighest Single Agent (HSA) Score: 1.95

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Estramustine

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

Estramustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estramustine binding protein (EMBP)	TTSBFYK	NOUNIPROTAC	Binder	[4]

Estramustine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]

Estramustine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[6]

Indication(s) of FORMESTANE

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Withdrawn from market	[3]

FORMESTANE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[7]

FORMESTANE Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[8]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Decreases Activity	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCIDBD9	MOLT-4	Investigative	[10]
Childhood T acute lymphoblastic leukemia	DCQETTW	CCRF-CEM	Investigative	[10]
Chronic myelogenous leukemia	DCW6Q0R	K-562	Investigative	[10]
Clear cell renal cell carcinoma	DCF9JZN	786-0	Investigative	[10]
Renal cell carcinoma	DCH0NXT	SN12C	Investigative	[10]
Cutaneous melanoma	DCC5T5D	SK-MEL-5	Investigative	[11]
Malignant melanoma	DC461Y6	LOX IMVI	Investigative	[11]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
• [5] Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol. 2003 May;169(5):1729-34.
• [6] Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
• [7] The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [9] 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.
• [10] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [11] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976