Differential profiles of HDAC1 substrates and associated proteins in breast cancer cells revealed by trapping

Histone deacetylase (HDAC) proteins, which regulate the acetylation state of proteins, are the targets of multiple clinical drugs for cancer treatment. Due to the heterogeneity of tumors, HDAC proteins play...

Development of an ELISA-Based HDAC Activity Assay for Characterization of Isoform-Selective Inhibitors

Histone deacetylase (HDAC) proteins are promising targets for cancer treatment, with several HDAC inhibitors used clinically as anticancer drugs. Most HDAC inhibitors nonspecifically interact with all or many of the 11 HDAC isoforms. Isoform-selective HDAC inhibitors would be useful tools to dissect the individual functions of HDAC proteins in cancer formation, in addition to potentially displaying effective anticancer properties. We report here a robust HDAC activity assay for screening selective HDAC inhibitors, which is inspired by the traditional enzyme-linked immunosorbent assay (ELISA). The key feature of the ELISA-based HDAC activity assay is use of mammalian cell–derived HDAC isoforms instead of recombinant proteins. Importantly, the assay was validated with several known HDAC inhibitors. The ELISA-based HDAC activity assay will facilitate the characterization of isoform-selective HDAC inhibitors against mammalian cell–derived HDAC proteins, which will enhance HDAC-centered cancer research and provide a foundation for anticancer drug development.

The structure based design of dual HDAC/BET inhibitors as novel epigenetic probes

DUAL946 (1) inhibits BET and HDAC proteins in chemoproteomic cell lysate experiments and in immune and cancer cells.