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ID: ALA1143185
Journal: Bioorg Med Chem Lett
Title: Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2).
Authors: Methot JL, Chakravarty PK, Chenard M, Close J, Cruz JC, Dahlberg WK, Fleming J, Hamblett CL, Hamill JE, Harrington P, Harsch A, Heidebrecht R, Hughes B, Jung J, Kenific CM, Kral AM, Meinke PT, Middleton RE, Ozerova N, Sloman DL, Stanton MG, Szewczak AA, Tyagarajan S, Witter DJ, Secrist JP, Miller TA.
Abstract: We report herein the initial exploration of novel selective HDAC1/HDAC2 inhibitors (SHI-1:2). Optimized SHI-1:2 structures exhibit enhanced intrinsic activity against HDAC1 and HDAC2, and are greater than 100-fold selective versus other HDACs, including HDAC3. Based on the SAR of these agents and our current understanding of the HDAC active site, we postulate that the SHI-1:2 extend the existing HDAC inhibitor pharmacophore to include an internal binding domain.
CiteXplore: 18182289