Stefan Knapp

Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He remains associated to the SGC as a visiting Professor at Oxford and he is also adjunct Professor of the George Washington University. Since 2017 he is the CSO of the newly founded SGC node at the Goethe-University Frankfurt.

Webinar summary: Small molecule degraders, such as protein targeting chimera (PROTACs), have emerged as a promising new pharmacological modality that has recently entered clinical trials. The catalytic properties of PROTACs, which act as chemical degraders of proteins of interest (POIs), represent an attractive new mechanism for drug development. However, the development and characterization of PROTACs, compared to conventional small molecules, requires a number of tailored assay systems that follow the degradation pathway and highlight critical steps for PROTAC optimization. I will discuss how PROTACs are designed based on their complex mechanism of action and how we are currently evaluating PROTACs as chemical tools. I will also present recent examples of target-selective PROTACs developed by our group and data from crystallographic fragment screening campaigns leading to initial ligands for new E3 ligases for the development of next-generation degraders.

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