Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors

HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failu...

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Bibliographic Details
Published in:Medicinal chemistry research 2023, Vol.32 (1), p.1-14
Main Authors: Faridoon, Zha, Yuqi Lavender, Zhang, Guiping, Li, Jie Jack
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Congestive heart failure
Cytoplasm
Deacetylation
Fibrosis
Heart diseases
Histones
Hsp90 protein
Inflammatory diseases
Inhibitors
Inorganic Chemistry
Medicinal Chemistry
Microtubules
Neurodegenerative diseases
Oxadiazoles
Pain
Pharmacology/Toxicology
Review Article
Tubulin
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Summary:HDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-oxadiazoles, especially difluoromethyl 1,3,4-oxadiazoles, are promising HDAC6 inhibitors for the treatment of chronic diseases such as heart failure, neurodegenerative diseases, fibrosis, and pain. Graphical abstract
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-022-02987-8