Heat shock protein 90 (Hsp90) is highly conserved chaperone protein which plays vital roles in stabilization,
regulation and folding of client proteins in cancer cells. Client proteins are key macromolecules for carcinogenesis and
their maintenance (stabilization and protection from aggregation and misfolding) is provided by Hsp90 chaperone activity.
Hsp90 allows proliferation of cancer cells by keeping misfolded client proteins in their proper functional folded form and
suppresses apoptotic pathways for cancer cell survival. For this purpose, Hsp90 inhibitors have become an important
growing class of antitumor agents in pharmaceutical industry. To date, numerous compounds have been tested as anticancer
drugs in preclinical and clinical studies. Hsp90 inhibitors may be categorized into two main classes: natural and synthetic
inhibitors. In this review, we will discuss the general properties and structure of both natural inhibitors (geldanamycin,
17-AAG, 17-DMAG, herbimycin, radicicol, novobiocin, (-)-EGCG, derrubone, gedunin, celastrol and their derivatives)
and synthetic inhibitors (purine scaffold inhibitors, pyrazole scaffold inhibitors, SNX-2112, STA9090 and their derivatives)
along with their therapeutic strategies in many different cancer types.
Cancer, chaperone, client proteins, geldanamycin, Hsp90 inhibitors, Hsp90.
Cumhuriyet University, Faculty of Pharmacy, Department of Basic Sciences, Division of Biochemistry, Sivas, Turkey.