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Updated: Sep 27, 2025

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Synthesis and structure-activity relationship of thiol-based histone deacetylase 6 inhibitors
Zheng Guo1,2, Yi Zhang1,2, Ya Bao1,3
1Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, China.
Abstract:
Selective histone deacetylase 6 (HDAC6) inhibitors are safe and well-tolerated with less off-target effect. However, most available HDAC6 inhibitors contain hydroxamate as a zinc-binding group (ZBG), and their unfavorable pharmacokinetic properties along with potential genotoxicity limited wide application in diverse diseases. Therefore, we designed and synthesized a series of selective HDAC6 inhibitors utilizing thiol as the ZBG and discussed their structure-activity relationship based on molecular docking. In particular, compound 21, obtained by constantly step-by-step simplification and evolution based on Ricolinostat, a specific HDAC6 inhibitor in Phase II, unexpectedly showed high selectivity (29-fold) and moderate potency (73 nM). Utilizing pyrimidine as a linker in thiol-based HDAC6 inhibitors produces an utterly novel structure, which might display different pharmacokinetic properties and genotoxicity.
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