Title:Targeting Hsp90-Cdc37: A Promising Therapeutic Strategy by Inhibiting Hsp90 Chaperone Function
VOLUME: 18 ISSUE: 13
Author(s):Lei Wang, Li Li, Kai Gu, Xiao-Li Xu, Yuan Sun and Qi-Dong You*
Affiliation:Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, China Pharmaceutical University, Nanjing 210009
Keywords:Hsp90/Cdc37, protein-protein interaction, PPI inhibitors, targeting strategies, protein kinases.
Abstract:Background & Objective: The Hsp90 chaperone protein regulates the folding, maturation
and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered
into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of
side-effects so that none have reached to the market. During the regulation progress, numerous protein-
protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With
the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have
been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI
has been widely reported to associate with numerous protein kinases, making it a novel target for the
treatment of cancers.
Results and Conclusion: In this paper, we briefly review the strategies and modulators targeting
Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions
we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone
function.
