Objective

Small-molecule drug discovery has had an enormous positive impact in improving human health. New transformational small-molecule drugs continue to be discovered but much of the limelight is now being taken by biologics and the promise of gene therapy. This presentation will reflect on how innovation in small-molecule drug discovery has focused on improving the speed and quality of candidate molecule identification. It will then discuss some ambitious and exciting new areas that small-molecule drug discovery is starting to expand in to. In addition to briefly highlighting a selection of innovative approaches from the literature I will present work from GSK on two classes of hetero-bifunctional molecules; Antibody Recruiting Molecules (ARMs) and Proteolysis Targeting Chimeras(PROTACs). These molecules look and behave very differently to traditional small-molecule inhibitors and require an open mind to progress which is not confined by current best practice for small-molecule drug discovery. Data will be presented to illustrate the opportunities these molecules have in developing transformational new classes of medicines that can deliver very different pharmacology to inhibitors but nevertheless share many features of classic small-molecule drug discovery