Discovery of First Histone Deacetylase 10 Fluorescent Probe

Histone deacetylase 10 (HDAC10) is an understudied member of the HDAC enzyme family, with its biological functions just beginning to be elucidated. Recent studies showed that HDAC10 is involved in key cellular processes and may contribute to disease pathology. However, no selective fluorescent probes for HDAC10 have been reported. This study presents the first series of HADC10-targeted fluorescent probes based on naphthalimide scaffold, in which probe 6 shows the most promising characteristics. It displays moderate inhibitory potency against HDAC10 (IC50 = 61.9 nM) and features a distinct pH-responsive fluorescent switch at pH 6.1. Live-cell imaging in HEK293T cells shows that probe 6 has good permeability, efficient cellular uptake, and effective HDAC10 target engagement, indicating its potential for biological applications. This probe provides an effective tool to investigate the role of HDAC10 in disease pathology and a basis for developing novel HDAC10-specific diagnostics and therapeutics.