Structural Requirements of Histone Deacetylase Inhibitors: SAHA Analogs Modified on the Hydroxamic Acid.

ABSTRACT: Histone deacetylase (HDAC) proteins have emerged as targets for anti-cancer therapeutics, with several inhibitors used in the clinic, including suberoylanilide hydroxamic acid (SAHA, vorinostat). Because SAHA and many other inhibitors target all or most of the 11 human HDAC proteins, the creation of selective inhibitors has been studied intensely. Recently, inhibitors selective for HDAC1 and HDAC2 were reported where selectivity was attributed to interactions between substituents on the metal binding moiety of the inhibitor and residues in the 14-Å internal cavity of the HDAC enzyme structure. Based on this earlier work, we synthesized and tested SAHA analogs with substituents on the hydroxamic acid metal binding moiety. The N-substituted SAHA analogs displayed reduced potency and solubili

SUBMITTER: Bieliauskas AV 

PROVIDER: S-EPMC6927578 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature