HDAC inhibitors: a 2013–2017 patent survey

ABSTRACT

Introduction: Zinc-dependent histone deacetylases (HDAC) inhibitors represent an important class of biologically active compounds with four of them approved by the FDA. A wide range of molecules has been reported for applications in several human diseases.Area covered: This review covers recent efforts in the synthesis and applications of HDAC inhibitors from 2013-2017.Expert opinion: HDAC inhibitors represent an important class of biologically active compounds for single or combination therapies. The current synthetic methodologies are oriented towards selective HDAC isoforms to achieve better therapeutic effects. Among the recent patents available, most of them focus on HDAC6 selective inhibitors. Beside this search for isoform selectivity, the quest for zinc binding groups with better pharmacokinetic properties and high potency against HDACs only motivates medicinal chemists, as well as the design of inhibitors targeting HDACs and at the same time another biological target. If the major applications are for anticancer activity, one can note the emerging applications in neurological or metabolic disorders or for the stimulation of the immune system.

KEYWORDS:

• Epigenetics
• cancer
• histone deacetylases
• inhibitors
• synthesis
• biological data

Article highlights

• Zinc-dependant HDAC inhibitors are described

• Most compounds bear a hydroxamic acid as the zinc-binding group

• HDAC6 selective inhibitors are the most described

• Nanomolar inhibition is generally obtained, and only few compounds showed picomolar activity

• The majority of assays used to validate the activity are enzymatic ones.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank the Centre National de la Recherche Scientifique, University of Poitiers, Region Poitou-Charentes, the Ligue Contre le Cancer: committee of Charente-Maritime and COST Action TD1406 for financial support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper has not been funded.