Kinetically Selective Inhibitors of Histone Deacetylase 2 (HDAC2) as Cognition Enhancers.

ABSTRACT: Aiming towards the development of novel nootropic therapeutics to address the cognitive impairment common to a range of brain disorders, we set out to develop highly selective small molecule inhibitors of HDAC2, a chromatin modifying histone deacetylase implicated in memory formation and synaptic plasticity. Novel ortho-aminoanilide inhibitors were designed and evaluated for their ability to selectively inhibit HDAC2 versus the other Class I HDACs. Kinetic and thermodynamic binding properties were essential elements of our design strategy and two novel classes of ortho-aminoanilides, that exhibit kinetic selectivity (biased residence time) for HDAC2 versus the highly homologous isoform HDAC1, were identified. These kinetically selective HDAC2 inhibitors (BRD6688 and

SUBMITTER: Wagner FF 

PROVIDER: S-EPMC4310013 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature