ABSTRACT
Support is requested for a Keystone Symposia conference entitled Targeted Protein Degradation, organized by
Drs. Rajesh Chopra, Nathanael Gray, Anita Gandhi and Georg Winter. The conference will be held in
Snowbird, Utah from March 29- April 1, 2020.
This Keystone Symposia conference will highlight the recent exciting advances in targeting proteins for
degradation as an alternative to conventional inhibitory small molecules and antibodies. Protein degradation
can be undertaken by bifunctional molecules that bind the target for ubiquitin-mediated degradation by
complexing them with Cereblon (CRBN), von Hippel-Lindau or other E3 ligases. Alternatively, ligase receptors
such as CRBN or DCAF15 can also be used as a ‘template’ to bind IMiD or sulphonamide-like compounds to
degrade multiple context specific proteins by the selected E3 ligases. The ‘template approach’ results in the
degradation of neo-substrates, some of which would be difficult to drug using conventional approaches.
The chemical properties necessary for drug discovery, the rules by which neo-substrates are selected by
ligase receptors and defining the optimal components of the ubiquitin proteasome for protein degradation are
still to be fully elucidated. This conference will bring together early pioneers in the field, emerging scientists and
experts from industry and academics to describe how these challenges are being addressed. Furthermore,
experts who have used IMiD agents and proteasome inhibition in the clinic in real world practical applications
of protein degradation agents have been invited to speak at this conference. Another unique aspect of this
conference is with it being paired with the Keystone Symposia conference on Ubiquitin Biology. Protein
ubiquitination regulates nearly every critical cellular pathway and emerging evidence has demonstrated that
defects within the ubiquitin proteasome system can directly lead to human disease. This has fueled a recent
expansion of drug development efforts to harness the ubiquitin proteasome system to both aid in its
functionality during disease progression and to specify individual targets for degradation. By pairing these
meetings, participants will be able to network and foster new collaborations between these two related areas of
science.