Rational discovery of selective inhibitors and degraders of the polyamine deacetylase HDAC10

DRA lecture held by Dr. Aubry Miller, German Cancer Research Center (DKFZ), Heidelberg, Germany

The enzyme family of histone deacetylases (HDACs) is a rich source of drug targets with five HDAC inhibitors approved for cancer therapy. The class IIb isozyme HDAC10 induces autophagy and mediates DNA damage repair, and HDAC10 knockdown/inhibition renders otherwise resistant neuroblastoma cells sensitive to chemotherapy treatment. HDAC10 also has an enigmatic catalytic function: it functions as a polyamine deacetylase, while being a poor lysine deacetylase. In spite of the potential therapeutic promise of HDAC10 inhibitors, and perhaps because of its unexpected catalytic behavior, HDC10 has received little attention from the chemical biology and medicinal chemistry community. Over the past few years, we have established a broad program to discover selective HDAC10 chemical probes and degraders. My lecture will detail our work in this area and our approaches to use them to validate the role(s) of HDAC10 not only in cancer development, but also in metabolism, immune function, and development.

The lecture is organised on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy, by Professor Christian A. Olsen, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen.

The DRA lecture is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.