Recent advances in the discovery of potent and selective HDAC6 inhibitors

Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2018-01, Vol.143, p.1406-1418
Main Authors: Wang, Xiu-Xiu, Wan, Ren-Zhong, Liu, Zhao-Peng
Format: Article
Language:English
Subjects:
HDAC6
HDAC6 inhibitors
Hydroxamic acids
Sulfur containing ZBGs
Zinc binding groups
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Summary:Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein trafficking and degradation, cell shape and migration. Selective HDAC6 inhibitors are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Therefore, extensive investigations have been made in the discovery of selective HDAC6 inhibitors. Based on their different zinc binding groups (ZBGs), in this review, HDAC6 inhibitors are grouped as hydroxamic acids, a sulfur containing ZBG based derivatives and other ZBG-derived compounds, and their enzymatic inhibitory activity, selectivity and other biological activities are introduced and summarized. [Display omitted] •Recent advances in the development of selective HDAC6 inhibitors were summarized.•Hydroxamic acid-based selective HDAC6 inhibitors.•A sulfur containing ZBG based selective HDAC6 inhibitors.•Other ZBG-derived selective HDAC6 inhibitors.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2017.10.040