Induced Proximity Drug Modalities: Hijacking Mother Nature to Control Protein Function

Craig Crews is the American Cancer Professor of Molecular, Cellular, and Developmental Biology, and also holds joint appointments in the departments of Chemistry and Pharmacology. His research interests focus on chemical biology, particularly on controlled proteostasis. Crews is a pioneer in the field of targeted protein degradation and his lab's research led to the development of the anti-cancer drug carfilzomib (Kyprolis). In addition, he has developed a new therapeutic modality (PROTACs) and Arvinas, a company he founded in 2013, has developed the first PROTAC for breast cancer, which has finished Phase 3 clinical trials and is currently awaiting FDA approval. Professor Craig Crews holds various distinctive and prestigious awards such as the 2025 Passano Award, 2024 Kimberly Prize (Northwestern University), 2023 Gabbay Prize (Brandeis University), 2021 Scheele Award of the Swedish Pharmaceutical Society, 2020 Heinrich Wieland Prize (Boehringer Ingelheim Foundation), and 2018: Royal Society of Chemistry Khorana Prize.

About the Lecture

My lab uses ‘Applied Chemical Biology’ to develop novel therapeutic modalities.  Enzyme inhibition has proven to be a successful paradigm for pharmaceutical development, however, it has several limitations.  Alternatively, for the past 25+ years, my lab has focused on developing Proteolysis Targeting Chimera (PROTAC), a new ‘controlled proteolysis’ technology that overcomes the limitations of the current inhibitor pharmacological paradigm. Based on an ‘Event-driven’ paradigm, PROTACs offer a novel, catalytic mechanism to irreversibly inhibit protein function, namely, the intracellular destruction of target proteins. This approach employs heterobifunctional molecules capable of recruiting target proteins to the cellular quality control machinery, thus leading to their degradation. More recently, we have developed RIPTACs to exploit heterobiofunctional mediated neo-PPIs to elicit tumor-specific 'super occupancy‘ of essential proteins, leading to tumor cell death.