Professor Dr Craig M. Crews, Heinrich Wieland Laureate 2020
Yale University, New Haven, CT, USA
Craig M. Crews is honoured with the 2020 Heinrich Wieland Prize for pioneering targeted protein degradation as a new therapeutic principle in pharmacology. In his early work, Craig M. Crews focused on blocking the cell's protein degradation machinery, the proteasome. He discovered how epoxomicin, a small molecule that inhibits the proteasome, functions and developed the first total synthesis of it. Based on synthetic derivatives of epoxomicin, Craig M. Crews co-founded his first company, Proteolix, whose proteasome inhibitor KyprolisTM received FDA approval for the treatment of multiple myeloma. In parallel, Craig M. Crews conceived of and demonstrated proof-of-concept of an entirely new approach to control protein levels in cells: the so-called PROTAC technology (PROteolysis TArgeting Chimera). PROTACs are small dimeric molecules that can be tailored to bind to different molecules in the cell. When they do so, they tether them to the intracellular protein degradation machinery for destruction. In contrast, traditional small molecule drugs only inhibit their targets. PROTACs are therefore the first class of molecules that can also act on those proteins of a cell that are not catalytically active, opening a whole range of possible treatments. the first PROTACs are already in clinical trials by the Yale-based company Arvinas, which Craig M. Crews founded a few years ago. They target the androgen and estrogen receptors in patients with metastatic prostate and breast cancer.
Craig M. Crews studied Chemistry at the University of Virginia in Charlottesville, USA, and received his PhD in Biochemistry from Harvard University in Cambridge, USA, in 1993. After two years as a postdoctoral researcher at Harvard University, he joined the faculty at Yale University in New Haven, USA, as Assistant Professor, and was promoted to Associate Professor in 2000. Crews founded his first company, Proteolix, in 2003 and in the same year, became Executive Director of the Yale Center for Molecular Discovery. He is a full professor since 2007, and has been appointed the John C. Malone Professor of Molecular, Cellular, and Developmental Biology with joint appointments in the departments of Chemistry and Pharmacology at Yale University. He is the Chief Scientific Advisor of Arvinas, which he founded in 2013. Craig M. Crews received many awards including the Khorana Prize of the Royal Society of Chemistry, the Award for Outstanding Achievement in Chemistry in Cancer Research by the American Association for Cancer Research, the UCB Ehrlich Award for Excellence in Medicinal Chemistry, and the Friedrich Wilhelm Bessel Research Award by the Alexander von Humboldt Foundation. He is a fellow of the Royal Society of Chemistry and the American Association for the Advancement of Science.