General Information of Drug Combination (ID: DCQI2O1)

Drug Combination Name
MK-5108 SNX-2112
Indication
Disease Entry Status REF
Breast carcinoma Investigative [1]
Component Drugs MK-5108   DMFGYKS SNX-2112   DMB5A80
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: OCUBM
Zero Interaction Potency (ZIP) Score: 7.52
Bliss Independence Score: 7.85
Loewe Additivity Score: 1.54
LHighest Single Agent (HSA) Score: 9.7

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]
Carcinoma DCEW1R4 EFM192B 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.