Xudong Cao, Zhiyuan Fan, Lingfang Xu, Wenchao Zhao, Haoran Zhang, Yunfang Yang, Ying Ren, Yuxian Xiao, Nan Zhou, Long Yin, Xueyan Zhou, Xu Zhu, Dong Guo
Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM)...
April 18, 2024: European Journal of Medicinal Chemistry