Discovery of Selective Histone Deacetylase 1 and 2 Inhibitors: Screening of a Focused Library Constructed by Click Chemistry, Kinetic Binding Analysis, and Biological Evaluation
Yukihiro Itoh,
Peng Zhan,
Toshifumi Tojo
et al.
Abstract:Histone deacetylase 1 and 2 (HDAC1/2) inhibitors are
potentially
useful as tools for probing the biological functions of the isoforms
and as therapeutic agents for cancer and neurodegenerative disorders.
To discover potent and selective inhibitors, we screened a focused
library synthesized by using click chemistry and obtained KPZ560 as an HDAC1/2-selective inhibitor. Kinetic binding analysis revealed
that KPZ560 inhibits HDAC2 through a two-step slow-binding
mechanism. In cellular assays, KPZ560 induced a dos… Show more
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