Structural determinants of affinity and selectivity in the binding of inhibitors to histone deacetylase 6.

Structural determinants of affinity and selectivity in the binding of inhibitors to histone deacetylase 6.
Bioorg Med Chem Lett. 2020 Feb 11;:127023
Authors: Osko JD, Christianson DW
Abstract
Histone deacetylase 6 (HDAC6) is associated with multiple neurological disorders as well as aggressive cancers, making its selective inhibition highly desirable for therapeutic purposes. The basic molecular design of an effective HDAC6 inhibitor consists of a zinc-binding group, a linker, and a capping group capable of making interactions at the mouth of the active site. To date, more than 50 high-resolution X-ray crystal structures of HDAC6-inhibitor complexes have been reported, many of which reveal intermolecular interactions that contribute to isozyme affinity and selectivity. Here, we review the key features of HDAC6 inhibitor design illuminated by these structural studies.
PMID: 32067866 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - February 10, 2020 Category: Chemistry Authors: Osko JD, Christianson DW Tags: Bioorg Med Chem Lett Source Type: research