Analysis and Recent Progress of Inhibition Strategies for the Molecular Chaperone HSP90

The molecular chaperone heat shock protein (HSP)90 plays a crucial role in protein folding, cell signal transduction, and maintenance of cellular homeostasis. Its dysfunction is closely related to the occurrence and development of various diseases such as tumors, making it an important target in the field of drug development. This article reviews the evolution of HSP90 inhibition strategies and the latest research progress, and systematically classifies the reported small molecule HSP90 inhibitors into 4 generations for a comprehensive summary. By elaborating on the design strategies, chemical structure characteristics, and action mechanisms of representative molecules of each generation of inhibitors, it analyzes in depth the core issues existing in the current research and development of HSP90 inhibitors, with a prospect of the future research directions, aiming to provide scientific ideas and research inspiration for the design of small molecule inhibitors targeting HSP90.