Details of the Drug Combination

General Information of Drug Combination (ID: DCUSUS6)

Drug Combination Name

Estramustine SNX-2112

Indication

Disease Entry	Status	REF
Non small cell carcinoma	Investigative	[1]

Component Drugs

Estramustine DMWTAOI

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: SKMES1

Zero Interaction Potency (ZIP) Score: 2.54

Bliss Independence Score: 1.04

Loewe Additivity Score: 0.75

LHighest Single Agent (HSA) Score: 4.5

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

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]
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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]
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Estramustine Interacts with 2 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]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[7]
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Indication(s) of SNX-2112

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

SNX-2112 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Heat shock protein 90 alpha (HSP90A)	TT78R5H	HS90A_HUMAN	Inhibitor	[3]
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SNX-2112 Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Decreases Expression	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[8]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[8]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[8]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[8]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[8]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[8]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[8]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[8]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[8]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[8]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[8]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[8]
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⏷ Show the Full List of 14 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCFQHPV	ES2	Investigative	[9]
Breast and ovarian cancer syndrome	DC2FA0Q	UWB1289	Investigative	[10]
Breast carcinoma	DCHGXC1	OCUBM	Investigative	[10]
Carcinoma	DC8ODZZ	EFM192B	Investigative	[10]
Colon adenocarcinoma	DCUBY2F	LOVO	Investigative	[10]
Invasive ductal carcinoma	DCASG5S	T-47D	Investigative	[10]
Adenocarcinoma	DCY7NYM	CAOV3	Investigative	[1]
Adenocarcinoma	DCWAD34	OVCAR3	Investigative	[1]
Adenocarcinoma	DCD6V9Z	NCIH2122	Investigative	[1]
Adenocarcinoma	DCT8LM1	COLO320DM	Investigative	[1]
Adenocarcinoma	DCSG1M5	DLD1	Investigative	[1]
Amelanotic melanoma	DCP3NN8	A2058	Investigative	[1]
Malignant melanoma	DCYVWGR	A375	Investigative	[1]
Malignant melanoma	DCWXPPS	RPMI7951	Investigative	[1]
Malignant melanoma	DC78TZX	SKMEL30	Investigative	[1]
Mesothelioma	DC04W3O	MSTO	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCLH11P	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCBLV7H	SK-OV-3	Investigative	[1]
Prostate carcinoma	DCAGN5S	VCAP	Investigative	[1]
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⏷ Show the Full List of 19 DrugCom(s)

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	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
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	Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2. J Neurooncol. 2001 Aug;54(1):23-9. doi: 10.1023/a:1012566601485.
8	The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-B and disruption of mitochondria-dependent pathways. Chem Biol Interact. 2013 Sep 5;205(1):1-10. doi: 10.1016/j.cbi.2013.06.007. Epub 2013 Jun 15.
9	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.
10	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.