Department Seminar

Upcoming Seminar

Histone Deacetylase Enzymes: Anti-cancer Drug Design
Dr. Mary Kay Pflum, Wayne State University

May 4, 2022
4:00pm in HSCI-105

Histone deacetylase (HDAC) enzymes are key players in cancer progression and have emerged recently as targets for anti-cancer drugs. In fact, four drugs are currently used clinically to treat leukemia and lymphoma. Despite the successes of HDAC inhibitors as therapeutics, the clinical drugs manifest significant side effects. One factor leading to the clinical side effects is the non-specific inhibition of the eleven HDAC proteins (HDAC1 – HDAC11) in human cells. There is still a lack of selective inhibitor compounds targeting only select HDAC proteins among the eleven HDAC family members, which could overcome side effect issues. Beyond drug design, selective inhibitor compounds as useful biomedical tools to study the biological functions of HDAC enzymes in normal biology and cancer. The goal is this project is to identify inhibitors that selectively target only one or only a few HDAC enzymes. Towards this goal, we have synthesized a variety of small molecule HDAC inhibitors and evaluated their potencies. In this talk, the identification of dual HDAC6/HDAC8-selective inhibitors is highlighted (see Negmeldin et al. Eur. J. Med Chem, 2018, 143, 1790-1806). Through inhibitor development, the HDAC project in the Pflum lab will deepen our understanding of cancer onset and progression, while also assisting in the development of next generation cancer therapeutics.