Identification of a new class of proteasome inhibitors based on a naphthyl-azotricyclic-urea-phenyl scaffold.

ABSTRACT: Proteasomes play an important role in protein degradation and regulation of many cellular pathways by maintaining protein balance. Inhibitors of proteasomes disrupt this balance affecting proteins that are key in malignancies and as such have found applications in the treatment of multiple myeloma and mantle cell lymphoma. However, resistance mechanisms have been reported for these proteasome inhibitors including mutations at the β5 site which necessitates the constant development of new inhibitors. In this work, we report the identification of a new class of proteasome inhibitors, polycyclic molecules bearing a naphthyl-azotricyclic-urea-phenyl scaffold, from screening of the ZINC library of natural products. The most potent of these compounds showed evidence of dose dependency through pr

SUBMITTER: Allardyce D 

PROVIDER: S-EPMC10034219 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature