Details of the Drug Combination

General Information of Drug Combination (ID: DCW3GE1)

Drug Combination Name

MK-5108 SNX-2112

Indication

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

Component Drugs

MK-5108 DMFGYKS

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: ES2

Zero Interaction Potency (ZIP) Score: 0.7

Bliss Independence Score: 7.98

Loewe Additivity Score: 4.62

LHighest Single Agent (HSA) Score: 9.38

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of MK-5108

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

MK-5108 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Inhibitor	[4]
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Inhibitor	[4]
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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	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[5]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[5]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[5]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[5]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[5]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[5]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[5]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[5]
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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	DC4KNFP	UWB1289	Investigative	[6]
Breast carcinoma	DCQI2O1	OCUBM	Investigative	[6]
Carcinoma	DCEW1R4	EFM192B	Investigative	[6]
Carcinoma	DCIZUBV	MDAMB436	Investigative	[6]
Colon adenocarcinoma	DC4DE8O	LOVO	Investigative	[6]
Invasive ductal carcinoma	DCC6SSF	T-47D	Investigative	[6]
Adenocarcinoma	DCN2TZ2	OVCAR3	Investigative	[7]
Adenocarcinoma	DC10PCM	A427	Investigative	[7]
Adenocarcinoma	DCBQ63R	DLD1	Investigative	[7]
Adenocarcinoma	DCFPC6I	SW-620	Investigative	[7]
Large cell lung carcinoma	DC7OKSR	NCI-H460	Investigative	[7]
Malignant melanoma	DCTG90W	SKMEL30	Investigative	[7]
Malignant melanoma	DCA3NDS	UACC62	Investigative	[7]
Non small cell carcinoma	DCEITKI	SKMES1	Investigative	[7]
Ovarian endometrioid adenocarcinoma	DCXBU3F	A2780	Investigative	[7]
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⏷ Show the Full List of 15 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	ClinicalTrials.gov (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
3	Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
4	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.
5	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.
6	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.
7	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.