Details of the Drug Combination

General Information of Drug Combination (ID: DCEW1R4)

Drug Combination Name

MK-5108 SNX-2112

Indication

Disease Entry	Status	REF
Carcinoma	Investigative	[1]

Component Drugs

MK-5108 DMFGYKS

SNX-2112 DMB5A80

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: EFM192B

Zero Interaction Potency (ZIP) Score: 0.96

Bliss Independence Score: 1.22

Loewe Additivity Score: 3.3

LHighest Single Agent (HSA) Score: 6.21

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
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCW3GE1	ES2	Investigative	[6]
Breast and ovarian cancer syndrome	DC4KNFP	UWB1289	Investigative	[1]
Breast carcinoma	DCQI2O1	OCUBM	Investigative	[1]
Carcinoma	DCIZUBV	MDAMB436	Investigative	[1]
Colon adenocarcinoma	DC4DE8O	LOVO	Investigative	[1]
Invasive ductal carcinoma	DCC6SSF	T-47D	Investigative	[1]
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	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	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	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.
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.