Antitumor potential of the protein phosphatase inhibitor, cantharidin, and selected derivatives

Cantharidin is a potent natural protein phosphatase monoterpene anhydride inhibitor secreted by several species of blister beetle, with its demethylated anhydride analogue, (S)-palasonin, occurring as a constituent of the higher plant Butea frondosa. Cantharidin shows both potent protein phosphatase inhibitory and cancer cell cytotoxic activities, but possible preclinical development of this anhydride has been limited thus far by its toxicity. Thus, several synthetic derivatives of cantharidin have been prepared, of which some compounds exhibit improved antitumor potential and may have use as lead compounds. In the present review, the potential antitumor activity, structure-activity relationships, and development of cantharidin-based anticancer drug conjugates are summarized, with protein phosphatase-related and other types of mechanisms of action discussed. Protein phosphatases play a key role in the tumor microenvimnment, and thus described herein is also the potential for developing new tumor microenvimnment-targeted cancer chemotherapeutic agents, based on cantharidin and its naturally occurring analogues and synthetic derivatives.

Automated summary

Cantharidin, a potent natural protein phosphatase inhibitor, shows both protein phosphatase inhibitory and cancer cell cytotoxic activities. Synthetic derivatives of cantharidin have been prepared to improve antitumor potential, providing lead compounds for anticancer drug development.