Details of the Drug Combination

General Information of Drug Combination (ID: DC5488Q)

Drug Combination Name

MK-1775 SNX-2112

Indication

Disease Entry	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	Investigative	[1]

Component Drugs

MK-1775 DM3WDZ5

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: ES2

Zero Interaction Potency (ZIP) Score: 8.67

Bliss Independence Score: 6.27

Loewe Additivity Score: 3.39

LHighest Single Agent (HSA) Score: 7.9

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of MK-1775

MK-1775 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_HUMAN	Inhibitor	[6]
------------------------------------------------------------------------------------

MK-1775 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Phosphorylation	[5]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[5]
------------------------------------------------------------------------------------

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]
------------------------------------------------------------------------------------

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	[7]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[7]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[7]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[7]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[7]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[7]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[7]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[7]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[7]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[7]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[7]
------------------------------------------------------------------------------------


⏷ 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
Adenocarcinoma	DC9F99K	OVCAR3	Investigative	[1]
Adenocarcinoma	DCJRSKJ	COLO320DM	Investigative	[1]
Adenocarcinoma	DCR5JTN	DLD1	Investigative	[1]
Adenocarcinoma	DCB8F4X	HCT116	Investigative	[1]
Adenocarcinoma	DC0TTTP	SW-620	Investigative	[1]
Amelanotic melanoma	DCNDPZY	A2058	Investigative	[1]
Germ cell tumour	DC3DD90	PA1	Investigative	[1]
Large cell lung carcinoma	DCNMHLY	NCI-H460	Investigative	[1]
Malignant melanoma	DC1XKAO	RPMI7951	Investigative	[1]
Malignant melanoma	DCPFJWS	SKMEL30	Investigative	[1]
Mesothelioma	DCPHBT5	MSTO	Investigative	[1]
Non small cell carcinoma	DCRP09O	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCIQ3QC	A2780	Investigative	[1]
Prostate carcinoma	DCJ2KSI	VCAP	Investigative	[1]
Breast and ovarian cancer syndrome	DC1YOJN	UWB1289	Investigative	[8]
Breast and ovarian cancer syndrome	DCK7EQI	UWB1289+BRCA1	Investigative	[8]
Breast carcinoma	DCZJPC2	OCUBM	Investigative	[8]
Carcinoma	DC58QG1	EFM192B	Investigative	[8]
Colon adenocarcinoma	DCTN716	LOVO	Investigative	[8]
Colon carcinoma	DCUD15Z	RKO	Investigative	[8]
Invasive ductal carcinoma	DCRJJBK	T-47D	Investigative	[8]
------------------------------------------------------------------------------------


⏷ Show the Full List of 21 DrugCom(s)

References

1	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.
2	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: 7702).
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
5	Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
6	A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
7	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.
8	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.