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 microenvironment, and thus described herein is also the potential for developing new tumor microenvironment-targeted cancer chemotherapeutic agents, based on cantharidin and its naturally occurring analogues and synthetic derivatives.

斑蝥素是一种强效的天然蛋白磷酸酶单萜酸酐抑制剂，由几种水疱甲虫分泌，其去甲基酸酐类似物 ( S )-palasonin 作为高等植物叶荠的成分存在. 斑蝥素显示出有效的蛋白磷酸酶抑制和癌细胞细胞毒性活性，但迄今为止，这种酸酐的可能临床前开发受到其毒性的限制。因此，已经制备了几种斑蝥素的合成衍生物，其中一些化合物表现出改善的抗肿瘤潜力并可能用作先导化合物。在本综述中，总结了基于斑蝥素的抗癌药物偶联物的潜在抗肿瘤活性、构效关系和开发，并讨论了蛋白磷酸酶相关和其他类型的作用机制。蛋白磷酸酶在肿瘤微环境中起关键作用，因此本文描述的还有开发新的肿瘤微环境靶向癌症化疗剂的潜力，