靶向IIa类hdac:表型和抑制剂的见解

Title:Targeting Class IIa HDACs: Insights from Phenotypes and Inhibitors

Volume: 28 Issue: 42

关键词: 药物发现，表观遗传调控，表型，组蛋白去乙酰化酶，HDAC异构体，IIa类HDAC，抑制剂，催化域抑制剂。

摘要: This review summarizes key literature defining the phenotypes of individual class IIa HDAC proteins and compounds that selectively target their enzymatic catalytic domain (CD). The focus is on the effects of class IIa HDACs in physiological and pathological conditions, both in vitro and in vivo, and on their mode of action in regulating genes, upstream proteins and signaling pathways. Phenotype studies further demonstrate either beneficial or detrimental effects of silencing selected class IIa HDACs or their enzymatic properties. We also summarize the knowledge gained from structure-activity relationships of CD inhibitors as well as molecular mechanisms underpinning isozyme selectivity where crystal structures or modelling studies are available. Given that the number of genes affected by silencing class IIa HDACs is much smaller than class I, the role of gene regulation of class IIa HDACs could be much more selective. Since class IIa HDACs have restricted tissue distributions and multiple functions independent of their CD, targeting the CD of class IIa HDACs could lead to more selective therapeutic agents with significantly fewer side-effects than other HDAC ligands.

Cite this article as:

Targeting Class IIa HDACs: Insights from Phenotypes and Inhibitors, Current Medicinal Chemistry 2021; 28 (42) . https://dx.doi.org/10.2174/0929867328666210629160647