An updated patent review of histone deacetylase (HDAC) inhibitors in cancer (2020 – present)

ABSTRACTIntroduction Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC inhibitors in various cancer types has continued to develop for decades, bringing several novel HDAC inhibitors successfully into clinical trials. The combination use of HDAC inhibitors with other agents have also been developed and have demonstrated superior efficacy compared to that of monotherapy in recent studies. Hence, development of new anticancer treatment and therapeutic regimen is necessary.Areas covered This review summarizes a comprehensive review of the patent literature from 2020 to 2022 including HDAC inhibitors and their use as anticancer agents (searched from European Patent Office, 2020–2022). The approved and developing HDAC inhibitors are described. It also provides perspectives on the challenges and future opportunities.Expert opinion Although hundreds of clinical trials of HDAC inhibitors are still going on, the application for HDAC inhibitors has been limited at present . Not only in the anticancer treatment, but also non-oncology disease therapies are being investigated eagerly. Recently, applications of HDAC inhibitors in non-oncology diseases have also been revealed and proceeded to clinical trials. New indications for HDAC inhibitors are needed urgently in the future.KEYWORDS: cancer treatmentHDAC inhibitorshistone deacetylasehydroxamic acid derivativesnon-oncology Article highlights HDAC, an enzyme regulates the epigenetic modification and plays a crucial role in the biological functions, such as cell growth, differentiation, migration and survival. Hence, cancer therapy of HDAC inhibitors has also been continued to develop for decades.To date, five HDAC inhibitors have been approved for the treatment of various types of lymphoma and multiple myeloma.Based on the functional groups of chemical structure, the most common HDAC inhibitors are hydroxamic acid derivatives and benzamide derivatives. Novel structures have been designed, synthesized and evaluated their inhibitory activities in vitro and in vivo.The investigation of HDAC inhibitors in different indications or the distinct combination use for therapeutic regimen has been proposed vigorously in recent years. It may provide HDAC inhibitors an opportunity to open avenues to the next stage.Declaration of interestThe 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.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author Contribution StatementYi-Min Liu: for reference collecting and manuscript writing. Jing-Ping Liou: for confirming manuscript and managing progress.Data availability statementThe data that support the findings of this study are available in Pubmed at https://pubmed.ncbi.nlm.nih.gov. These data were derived from the following resources available in the public domain, European Patent Office at https://www.epo.org/.Additional informationFundingThis paper was funded by the Ministry of Science and Technology, Taiwan (MOST111-2113-M-038-004 and MOST110-2320-B-038-030).