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ID: ALA1140803
Journal: Bioorg Med Chem Lett
Title: Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2).
Authors: Witter DJ, Harrington P, Wilson KJ, Chenard M, Fleming JC, Haines B, Kral AM, Secrist JP, Miller TA.
Abstract: A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model.
CiteXplore: 18060775