Abstract IA1-2: Drugging oncogenic transcription factors

Abstract

Abstract One of the most vexing problems in life science is that of “undruggability,” the difficulty of targeting certain biological macromolecules in vivo using existing drug or ligand discovery technologies. It has been estimated that as many as 80% to 90% of all potential targets, including many that have been extensively validated in humans and in animal models, are undruggable. Among the most biologically validated and yet chemically intractable of all targets are transcription factors, master regulatory proteins that are inappropriately activated in a large percentage of human tumors. The Verdine laboratory is developing powerful new chemistry-based platform technologies to address undruggable targets, including transcription factors. Specifically, the lab is developing “synthetic biologics,” molecules that, like biologics, possess the ability to target large flat surfaces, but that, like small molecules, are fully synthetic and hence can be modified at will. Progress on the development of one class of synthetic biologics—hydrocarbon-stapled alpha-helical peptides—for use in targeting transcription factors will be reviewed in this talk.