2. Academic Validation
  3. Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2)

Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2)

  • Bioorg Med Chem Lett. 2008 Jan 15;18(2):726-31. doi: 10.1016/j.bmcl.2007.11.047.
David J Witter 1,  Paul Harrington,  Kevin J Wilson,  Melissa Chenard,  Judith C Fleming,  Brian Haines,  Astrid M Kral,  J Paul Secrist,  Thomas A Miller
Affiliations

Affiliation

  • 1 Department of Drug Design and Optimization-Medicinal Chemistry, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. [email protected]
PMID: 18060775 DOI: 10.1016/j.bmcl.2007.11.047
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.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-173160
    HDAC1/2 Inhibitor