1 research outputs found
Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors
Ubiquitin
specific protease 7 (USP7, HAUSP) has become an attractive
target in drug discovery due to the role it plays in modulating Mdm2
levels and consequently p53. Increasing interest in USP7 is emerging
due to its potential involvement in oncogenic pathways as well as
possible roles in both metabolic and immune disorders in addition
to viral infections. Potent, novel, and selective inhibitors of USP7
have been developed using both rational and structure-guided design
enabled by high-resolution cocrystallography. Initial hits were identified
via fragment-based screening, scaffold-hopping, and hybridization
exercises. Two distinct subseries are described along with associated
structure–activity relationship trends, as are initial efforts
aimed at developing compounds suitable for <i>in vivo</i> experiments. Overall, these discoveries will enable further research
into the wider biological role of USP7