Details of the Drug Combination

General Information of Drug Combination (ID: DCMAJJO)

Drug Combination Name
SNX-2112 Lomustine
Indication
Disease Entry Status REF
Malignant melanoma Investigative [1]
Component Drugs SNX-2112   DMB5A80 Lomustine   DMMWSUL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SKMEL30
Zero Interaction Potency (ZIP) Score: 2.53
Bliss Independence Score: 3.78
Loewe Additivity Score: 2.09
LHighest Single Agent (HSA) Score: 6.29

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of SNX-2112
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
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 [2]
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SNX-2112 Interacts with 6 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]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [5]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases 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]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Lomustine
Disease Entry ICD 11 Status REF
Brain cancer 2A00 Approved [3]
Central nervous system neoplasm N.A. Approved [4]
Primitive neuroectodermal tumor N.A. Approved [4]
Classic Hodgkin lymphoma N.A. Investigative [4]
Lomustine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Inhibitor [6]
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Lomustine Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [7]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [9]
DNA polymerase eta (POLH) OTN07WXU POLH_HUMAN Increases Expression [10]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Response To Substance [11]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DC891HL UWB1289 Investigative [12]
Breast carcinoma DCZUIVN OCUBM Investigative [12]
Invasive ductal carcinoma DCR784D T-47D Investigative [12]
Adenocarcinoma DC8CCTB NCIH2122 Investigative [1]
Adenocarcinoma DCSWL8L DLD1 Investigative [1]
Adenocarcinoma DCTGYZ1 HCT116 Investigative [1]
Amelanotic melanoma DCVRFLD A2058 Investigative [1]
Mesothelioma DCS3PQY MSTO Investigative [1]
Non small cell carcinoma DCW9LN8 SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DC7DPJ7 A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DC5POBB SK-OV-3 Investigative [1]
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⏷ Show the Full List of 11 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
2 Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
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: 7214).
4 Lomustine FDA Label
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 Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds. Acta Pol Pharm. 2007 Jan-Feb;64(1):27-33.
7 Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
8 High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.
9 Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
10 Translesion polymerase is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res. 2014 Oct 1;74(19):5585-96. doi: 10.1158/0008-5472.CAN-14-0953. Epub 2014 Aug 14.
11 Human osteosarcoma xenografts and their sensitivity to chemotherapy. Pathol Oncol Res. 2004;10(3):133-41. doi: 10.1007/BF03033741. Epub 2004 Sep 25.
12 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165