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- W1982327046 abstract "Long used as a prognostic indicator, the calcium binding protein, S100B, has been directly linked to Malignant Melanoma (MM). S100B binds the typically wild-type p53 tumor suppressor in MM and promotes its degradation. In order to restore p53 levels within MM along with its tumor suppressor and apoptotic activities, we have implemented a program for the discovery and optimization of S100B inhibitors (often referred to as SBiXs). In the process, we have uncovered and probed the three persistent binding sites within S100B. Liganding within these sites was characterized using structural biology techniques (NMR and X-ray crystallography) and inhibitor efficacy was evaluated using Fluorescent Polarization Competition Assays and cellular assays. Efforts to discover/synthesize and/or to improve existing inhibitors of S100B to restore p53 activity in human malignant melanoma are ongoing and SBiXs occupying the persistent binding Sites 1, 2, and 3 simultaneously are desired. Such compounds can then be examined for in vivo efficacy. The compounds presented offer potential bridging scaffolds between Sites 1, 2, and 3; and will act as the basis for the design of improved SBiXs. SBiXs may also have therapeutic value for treating other cancers with elevated S100B and wt p53 such as astrocytoma, renal tumors, and some forms of leukemia." @default.
- W1982327046 created "2016-06-24" @default.
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- W1982327046 date "2015-01-01" @default.
- W1982327046 modified "2023-09-28" @default.
- W1982327046 title "Targeting Melanoma with Small Molecules: Inhibitors of the Calcium-Binding Protein S100B" @default.
- W1982327046 doi "https://doi.org/10.1016/j.bpj.2014.11.1181" @default.
- W1982327046 hasPublicationYear "2015" @default.
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