Structure-Based Identification of Novel Histone Deacetylase 4 (HDAC4) Inhibitors.

ABSTRACT: Histone deacetylases (HDACs) are important cancer drug targets. Existing FDA-approved drugs target the catalytic pocket of HDACs, which is conserved across subfamilies (classes) of HDAC. However, engineering specificity is an important goal. Herein, we use molecular modeling approaches to identify and target potential novel pockets specific to Class IIA HDAC-HDAC4 at the interface between HDAC4 and the transcriptional corepressor component protein NCoR. These pockets were screened using an ensemble docking approach combined with consensus scoring to identify compounds with a different binding mechanism than the currently known HDAC modulators. Binding was compared in experimental assays between HDAC4 and HDAC3, which belong to a different family of HDACs. HDAC4 was significantly inhibited

SUBMITTER: Agarwal R 

PROVIDER: S-EPMC11279411 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature