Small Molecule Induced Protein Degradation - A New Drug Discovery Paradigm

Abstract: The development of new anti-cancer therapies continues to be massively outpaced by the rapidly expanding knowledge into the biological mechanisms that underpin the development of cancer.  One major obstacle is that many potentially interesting targets are challenging to drug.  This lecture will focus on strategies using covalent inhibitors and small molecule degraders which hold the promise of making many previously challenging targets druggable.  In particular, we will focus on the use of these approaches to target kinases and present some key advantages of small molecule degraders including potency, selectivity and abrogation of non-kinase activity dependent functions.  We will also describe efforts to target KRAS – a notorious and frequent oncogene that has been recalcitrant to small molecule approaches.