Student Hosted Colloquia: Professor Craig M. Crews, Yale University
Student Hosted Colloquia: Professor Craig M. Crews, Yale University (Host: Franco Faucher)
**This seminar is available for in-person attendance.**
"PROTACs and Targeted Protein Degradation: A New Therapeutic Modality"
About the Seminar
My lab is interested using ‘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. As an alternative, for the past 20 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. We have demonstrated the ability to degrade a wide variety of targets (kinases, transcription factors, epigenetic readers) with PROTACs at picomolar concentrations. Moreover, the PROTAC technology has been demonstrated with multiple E3 ubiquitin ligases and now two PROTAC-based drug candidates are being tested in Phase 2 clinical trials for prostate and breast cancer.
About the Speaker
Dr. 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. Dr. 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. 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) and an honorary doctoral degree from the Technische Universität Dortmund, Germany (doctor rerum naturalium honoris causa) (2021).
Image Credit: Karissa Van Tassel