Craig M. Crews

Craig M. Crews is the inventor of PROTAC (proteolysis-targeting chimera) technology, a revolutionary approach to drug discovery that exploits the cell's own ubiquitin-proteasome system to selectively degrade disease-causing proteins. His seminal 2001 paper in PNAS described the first proof-of-concept PROTAC molecule, establishing the conceptual and experimental foundation for an entire new therapeutic modality. Over the following two decades, Crews and his group at Yale systematically optimized PROTAC design principles — including linker chemistry, E3 ligase recruitment, binary complex formation, and cooperative ternary complex thermodynamics — transforming the concept into a clinically viable drug class. He co-founded Arvinas, Inc., which advanced the first two PROTAC molecules into clinical trials: ARV-110 (bavdegalutamide) targeting the androgen receptor in prostate cancer and ARV-471 (vepdegestrant) targeting the estrogen receptor in breast cancer. Beyond PROTACs, Crews has pioneered chemical tools to study proteasome biology, developed bifunctional molecules exploiting other E3 ligases including CRBN, VHL, and MDM2, and contributed foundational insights into protein homeostasis and cell signaling relevant to cancer. He is an elected member of the National Academy of Sciences and has received numerous honors including the Wolf Prize in Chemistry. His work has fundamentally reshaped how the pharmaceutical industry conceives of druggable targets.