Selective and nonselective HDAC8 inhibitors: a therapeutic patent review

Area of Science:

• Medicinal Chemistry
• Oncology
• Drug Discovery

Background:

• Histone deacetylase 8 (HDAC8) is overexpressed in various human cancers, making it a significant therapeutic target.
• HDAC8 inhibitors have demonstrated efficacy in treating both solid and hematological tumors, with several candidates progressing through clinical trials.
• Achieving selectivity for the HDAC8 enzyme remains a critical challenge in developing effective anticancer agents.

Purpose of the Study:

• To review patented selective and nonselective HDAC8 inhibitors.
• To discuss the implications of these inhibitors as anticancer agents.
• To highlight structural features, such as a fish-like arrangement, that enhance potency and selectivity for HDAC8.

Main Methods:

• Comprehensive analysis of patents related to HDAC8 inhibitors.
• Evaluation of molecular structures for their potential to impart potency and selectivity.
• Review of existing and emerging HDAC8 inhibitor candidates for anticancer applications.

Main Results:

• Identification of numerous patented HDAC8 inhibitors, encompassing both selective and nonselective compounds.
• Emphasis on a specific molecular architecture ('fish-like') as crucial for achieving desired potency and selectivity against HDAC8.
• The reviewed inhibitors show potential as anticancer agents, particularly in targeting cancers with HDAC8 overexpression.

Conclusions:

• The patent landscape reveals diverse strategies for HDAC8 inhibitor development.
• A modified fish-like structural motif is proposed as key for designing potent and selective HDAC8 inhibitors.
• This analysis provides insights for future development of targeted anticancer therapies focused on HDAC8.