Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK.
Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, UK.
Chem Commun (Camb). 2020 Apr 21;56(32):4476-4479. doi: 10.1039/d0cc01485k.
We have identified a proteolysis targeting chimera (PROTAC) of class I HDACs 1, 2 and 3. The most active degrader consists of a benzamide HDAC inhibitor, an alkyl linker, and the von Hippel-Lindau E3 ligand. Our PROTAC increased histone acetylation levels and compromised colon cancer HCT116 cell viability, establishing a degradation strategy as an alternative to class I HDAC inhibition.
我们鉴定了一个靶向 I 类组蛋白去乙酰化酶（HDACs）1、2 和 3 的蛋白水解靶向嵌合体（PROTAC）。最有效的降解物由苯甲酰胺 HDAC 抑制剂、烷基连接子和 von Hippel-Lindau E3 配体组成。我们的 PROTAC 增加了组蛋白乙酰化水平并损害结肠癌细胞 HCT116 的活力，建立了一种降解策略，作为 I 类 HDAC 抑制的替代方案。
