Details of the Drug Combination

General Information of Drug Combination (ID: DC0KO9R)

Drug Combination Name

GSK525762 SNX-2112

Indication

Disease Entry	Status	REF
Breast carcinoma	Investigative	[1]

Component Drugs

GSK525762 DMPAWBN

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

High-throughput Screening Result

Testing Cell Line: KPL1

Zero Interaction Potency (ZIP) Score: 0.98

Bliss Independence Score: 4.34

Loewe Additivity Score: 0.49

LHighest Single Agent (HSA) Score: 6.97

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of GSK525762

Disease Entry	ICD 11	Status	REF
Haematological malignancy	2B33.Y	Phase 1	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

GSK525762 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bromodomain-containing protein 4 (BRD4)	TTRA6BO	BRD4_HUMAN	Modulator	[6]
Bromodomain and extraterminal domain protein (BET)	TTE4BSY	NOUNIPROTAC	Inhibitor	[2]
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GSK525762 Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Increases Expression	[7]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[8]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Decreases Expression	[8]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[8]
Protein-lysine 6-oxidase (LOX)	OT1C2HIU	LYOX_HUMAN	Decreases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[9]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[9]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Expression	[5]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3)	OT25JBA3	F263_HUMAN	Increases Expression	[5]
Protein GREB1 (GREB1)	OTU6ZA26	GREB1_HUMAN	Decreases Expression	[8]
Endothelial PAS domain-containing protein 1 (EPAS1)	OTRE3O8U	EPAS1_HUMAN	Increases Expression	[5]
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⏷ Show the Full List of 11 DOT(s)

Indication(s) of SNX-2112

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[4]

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	[4]
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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	[10]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[10]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[10]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[10]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[10]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[10]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[10]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[10]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[10]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[10]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[10]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[10]
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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
Breast and ovarian cancer syndrome	DC5C6BK	UWB1289	Investigative	[1]
Breast and ovarian cancer syndrome	DCHVSGR	UWB1289+BRCA1	Investigative	[1]
Breast carcinoma	DCCY7DH	OCUBM	Investigative	[1]
Carcinoma	DCSQ1WS	MDAMB436	Investigative	[1]
Colon adenocarcinoma	DCVMBZL	LOVO	Investigative	[1]
Colon carcinoma	DCEPS8Q	RKO	Investigative	[1]
Invasive ductal carcinoma	DCPRQFF	T-47D	Investigative	[1]
Adenocarcinoma	DCGLFEH	CAOV3	Investigative	[11]
Adenocarcinoma	DC08Y9W	OVCAR3	Investigative	[11]
Adenocarcinoma	DC9MBPA	A427	Investigative	[11]
Adenocarcinoma	DCNY6I7	NCIH1650	Investigative	[11]
Adenocarcinoma	DCW35PO	COLO320DM	Investigative	[11]
Adenocarcinoma	DCNJJQ7	HCT116	Investigative	[11]
Malignant melanoma	DCUCACI	SKMEL30	Investigative	[11]
Mesothelioma	DCKIXMV	MSTO	Investigative	[11]
Prostate carcinoma	DCSB052	LNCAP	Investigative	[11]
Prostate carcinoma	DCFW3OD	VCAP	Investigative	[11]
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⏷ Show the Full List of 17 DrugCom(s)

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	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	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: 7033).
4	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
5	The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
6	Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
7	Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
8	An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
9	MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
10	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.
11	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.