Antitumor Effects of Celastrol and Semi-Synthetic Derivatives

Celastrol is a quinone methide triterpenoid extracted from the root bark of the Chinese medicine Tripterygium wilfordii with the most potent antitumor activity among the natural triterpenoids. Celastrol has the abilities to inhibit proliferation, induce apoptosis and suppress invasion and metastasis of tumor cells. Structure and activity analysis based on celastrol semi-synthetic derivatives revealed that the quinone methide moiety is required for its antitumor activity. The heat shock protein HSP90 chaperone machinery and NF-κB signaling are two principal pathways targeted by celastrol. The optimization of solubility and identification of tumor specific targets is required for further developing celastrol and its derivatives as clinically useful anticancer agents.