HDAC6: physiological function and its selective inhibitors for cancer treatment

Area of Science:

• Molecular Biology
• Epigenetics
• Cancer Research

Background:

• Histone acetylation and deacetylation regulate gene transcription.
• Histone deacetylase (HDAC) isoforms are cancer therapy targets.
• HDAC6, a unique isoform, is increasingly recognized for its roles in cancer.

Purpose of the Study:

• To review the structural elements and biological functions of HDAC6.
• To discuss recent selective inhibitors of HDAC6.
• To analyze the structure-activity and structure-selectivity relationships of HDAC6 inhibitors.

Main Methods:

• Literature review of HDAC6 structure, function, and inhibitors.
• Analysis of structure-activity relationships (SAR).
• Analysis of structure-selectivity relationships (SSR).

Main Results:

• HDAC6's unique structure and function involve tubulin, HSP90, invasin, and ubiquitin-protein.
• HDAC6 is implicated in tumorigenesis, development, and metastasis.
• Recent selective inhibitors show promise, with defined SAR and SSR.

Conclusions:

• HDAC6 is a significant target for cancer therapy due to its unique role.
• Understanding HDAC6's structure and inhibitor interactions is crucial for developing effective treatments.
• Selective HDAC6 inhibition offers a potential strategy to mitigate side effects associated with broader HDAC inhibition.