B06
Design of potent and selective USP25 and USP28 inhibitors
Project Summary
The deubiquitylase USP28 is a positive regulator of various cancer-driving cellular pathways and therefore considered a highly attractive target for the development of pharmacological cancer therapies. Further development of known inhibitors into clinically usable drugs is currently limited due to their bi-specificity for USP28 and its close homolog USP25 which acts as a central regulatory factor in various immune system related processes.
We aim to develop small-molecule USP28 and USP25 inhibitors with high potency and selectivity for one DUB over the other. To achieve this, we use a combination structural, biophysical and biochemical characterization together with in silico analysis and chemical synthesis to modify and combine existing inhibitor scaffolds and identify novel binding entities and sites. The designed compounds will provide new avenues to better understand USP28 and USP25 biology and a framework for the development of potent drugs with limited side effects.
