Criteria-guided selection of alternative zinc-binding groups of HDAC3 inhibitors using in silico and in vitro approaches.
Histone deacetylases (HDACs) are epigenetic enzymes linked to several biological functions and diseases. Class I HDACs (HDAC1-3) share high protein sequence and active site similarity. Hydroxamate-based inhibitors, while highly potent, are non-selective with poor pharmacokinetic profile, prompting exploration of altern...