OC-Kolloquium: Prof. Dr. A. Ganesan

Prof. Dr. A. Ganesan, University of East Anglia, Norwich, UK:

Epigenetic Drug Discovery: From Natural Product Total Synthesis to Dual Mechanism Inhibitors
There are three major epigenetic modifications that modulate eukaryotic gene transcription: DNA methylation and the methylation and acetylation of histone proteins. These reversible transformations are catalyzed by enzymes that have become important targets for drug discovery and nine ‘epidrugs’ are now approved for clinical use. In this lecture, I will describe my group’s efforts in this area beginning with the total syntheses of histone deacetylase (HDAC) natural product inhibitors spiruchostatin A, romidepsin and azumamides. I will then give recent examples of dual mechanism of action hybrids such as dual HDAC and lysine demethylase inhibitors and dual lysine methyltransferase and demethylase inhibitors.