HDAC6 is an emerging drug target as it has been correlated to a variety of pathologies such as autoimmune disorders, neurodegenerative diseases, and cancer. The genetic ablation of HDAC6 leads to viable and fertile animals and accordingly, the selective inhibition of the enzyme does not show cytotoxic effects normally associated with the inhibition of Class I HDAC isoforms.<br/>Enzymatic data, crystal structures and docking simulations of a class of benzohydroxamic acid-based compounds interacting with the zebrafish catalytic domain 2 of HDAC6 reveal the role of fluorination in the selectivity over class I isoforms. Intriguingly, the fluorination increases the residence time of the parent compound, which may be an important mechanism for sustained pharmacological inhibition of HDAC6. These findings point to a general strategy in the development of novel, HDAC6 selective inhibitors.

HDAC6: How to enhance the selectivity of benzohydroxamic acid-based inhibitors

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.