Trainee Talk at Dana Farber Targeted Protein Degradation

Abstract

Nimbolide, a naturally occurring anti-cancer compound, has been reported to bind the E3 ligase, RNF114. It covalently binds to Cys-8 present on its N-terminal. A bivalent degrader featuring Nimbolide (and EN219) and JQ1 (BET domain inhibitor) has been successfully employed in the degradation of BRD4. A detailed biochemical characterization of the degradation is already available. However, a structural model showing the ternary complex of RNF114-PROTAC-BRD4 is not available. In this work, we present a structural model of the ternary complex.

When: 17th February, 2022. 10:30 pm IST