Beyond the Selective Inhibition of Histone Deacetylase 6

Area of Science:

• Biochemistry
• Enzymology
• Drug Discovery

Background:

• Histone deacetylase 6 (HDAC6) removes acetyl groups from non-histone proteins like α-tubulin, Hsp90, and cortactin.
• HDAC6 plays a role in oncological, immunological, and neurological processes, making it a potential drug target.

Purpose of the Study:

• To review structure-activity and structure-selectivity relationships of HDAC6 inhibitors.
• To understand HDAC6 function and validate it as a drug target.

Main Methods:

• Analysis of structure-activity relationships (SAR) of HDAC6 inhibitors.
• Classification of inhibitors based on structural features (cap groups and linkers).

Main Results:

• HDAC6 inhibitors can be categorized into two main classes based on their structural characteristics.
• Detailed SAR and selectivity data for various HDAC6 inhibitors are presented.

Conclusions:

• Understanding SAR and selectivity is key to developing potent and selective HDAC6 inhibitors.
• Selective HDAC6 inhibitors hold promise for therapeutic applications in oncology, immunology, and neurology.