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

Bioorg Med Chem Lett. 2021 Feb 17:127857. doi: 10.1016/j.bmcl.2021.127857. Online ahead of print.ABSTRACTHeat 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.PMID:33609661 | DOI:10.1016/j.bmcl.2021.127857

Source: Bioorganic and Medicinal Chemistry Letters - February 20, 2021 Category: Chemistry Authors: Oi Wei Mak Nabangshu Sharma J óhannes Reynisson Ivanhoe K H Leung Source Type: research