H8-A5

Description

H8-A5 is a novel human histone deacetylase 8 HDAC8 inhibitor. A highly specific ZBG-based pharmacophore model was developed by incorporating a custom zinc-binding group ZBG feature. Pharmacophore-based virtual screening identified three novel HDAC8 inhibitors with low micromolar IC50 values 1.8-1.9 ?M . Further studies showed that H8-A5 was more selective for HDAC8 than HDAC1/4 and exhibited antiproliferative activity in MDA-MB-231 cancer cells. Molecular docking and molecular dynamics studies showed that H8-A5 could bind to HDAC8, providing a good starting point for the development of HDAC8 inhibitors for cancer treatment.