Discovery of novel Hsp90 C-terminal domain inhibitors that disrupt co-chaperone binding

Abstract

Heat shock protein 90 (Hsp90) is an essential molecular chaperone that performs vital stress-related and housekeeping functions in cells and is a current therapeutic target for diseases such as cancers. Particularly, the development of Hsp90 C-terminal domain (CTD) inhibitors is highly desirable as inhibitors that target the N-terminal nucleotide-binding domain may cause unwanted biological effects. Herein, we report on the discovery of two drug-like novel Hsp90 CTD inhibitors by using virtual screening and intrinsic protein fluorescence quenching binding assays, paving the way for future development of new therapies that employ molecular chaperone inhibitors.

Keywords: Cancer; Hsp90; Inhibitor; Molecular chaperone; Virtual screening.