The structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity.

ABSTRACT: Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for cancer treatment. Four HDAC inhibitors have been approved as anti-cancer therapeutics, including SAHA (Suberoylanilide hydroxamic acid, Vorinostat, Zolinza). SAHA is a nonselective HDAC inhibitor that targets most of the eleven HDAC isoforms. The nonselectivity of SAHA might account for its clinical side effects, but certainly limits its use as a chemical tool to study cancer-related HDAC cell biology. Herein, the nonselective HDAC inhibitor SAHA was modified at the C4 position of the linker to explore activity and selectivity. Several C4-

SUBMITTER: Negmeldin AT 

PROVIDER: S-EPMC5890937 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature