Discovery of new Hsp90-Cdc37 protein-protein interaction inhibitors: in silico screening and optimization of anticancer activity.

ABSTRACT: The interaction between heat shock protein 90 (Hsp90) and Hsp90 co-chaperone cell-division cycle 37 (Cdc37) is crucial for the folding and maturation of several oncogenic proteins, particularly protein kinases. This makes the inhibition of this protein-protein interaction (PPI) an interesting target for developing new anticancer compounds. However, due to the large interaction surface, developing PPI inhibitors is challenging. In this work, we describe the discovery of new Hsp90-Cdc37 PPI inhibitors using a ligand-based virtual screening approach. Initial hit compounds showed Hsp90 binding, resulting in anticancer activity in the MCF-7 breast cancer cell line. To optimize their antiproliferative effect, 35 analogs were prepared. Binding affinity for Hsp90 was determined for the most promis

SUBMITTER: Dernovsek J 

PROVIDER: S-EPMC11375794 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature