Lecture
Reedijk Symposium 2025: Induced Proximity Drug Modalities: Hijacking Mother Nature to Control Protein Function
- Date
- Friday 7 November 2025
- Time
- Location
-
Lecture Hall
Einsteinweg 57
2333 CC Leiden - Room
- C1
Abstract
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.
About Craig Crews
Craig Crews is the John C. Malone Professor of MCDB and professor of Chemistry and Pharmacology at Yale University. He graduated from the U. Virginia with a B.A. in Chemistry and received his Ph.D. from Harvard University in Biochemistry. On the faculty at Yale since 1995, his laboratory has developed the use of small molecules to control intracellular protein levels. In 2003, he co-founded Proteolix, Inc., whose proteasome inhibitor, Kyprolis™ received FDA approval for the treatment of multiple myeloma. The Crews’ lab is also credited with founding the field of ‘Targeted Protein Degradation’ drug development technology, i.e., PROTACs, which has the potential to target currently ‘undruggable’ disease causing proteins. In 2013, Dr. Crews launched the New Haven-based biotech venture, Arvinas, Inc., which is testing the first PROTAC-based drugs in clinical trials for prostate and breast cancer. Since then he has founded Halda Therapeutics, whose first RIPTAC entered clinical trials in 2025 for prostate cancer. Dr. Crews has received numerous awards and honors, including the Ehrlich Award for Medicinal Chemistry (2014), a NIH R35 Outstanding Investigator Award (2015), the AACR Award for Outstanding Achievement in Chemistry in Cancer Research (2017), the Khorana Prize from the Royal Society of Chemistry (2018), the Pierre Fabre Award for Therapeutic Innovation (2018), the Pharmacia-ASPET Award for Experimental Therapeutics (2019), the Heinrich Wieland Prize (2020), the Scheele Prize (2021), an honorary doctoral degree from the Technische Universität Dortmund, Germany (doctor rerum naturalium honoris causa) (2021), the Connecticut Medal of Technology (2022), the inaugural Bristol Myers Squibb Award in Enzyme Chemistry (2023), the Gabbay Prize with Ray Deshaies (2023), the Kimberly Prize (2024), Emanuel Merck Lectureship, the IUPAC-Richter Prize (2024), the Passano Award with Ray Deshaies (2025) and the Havinga Prize (2025).