CD147 is a transmembrane glycoprotein and a member of immunoglobulin superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6a could be used as the novel type of anticancer agent or as a part of the molecular biology research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.

CD147是一种跨膜糖蛋白，是免疫球蛋白超家族的成员，在黑素瘤细胞中强烈表达。CD147 在肿瘤发展中具有关键作用。因此，它是黑色素瘤的潜在药物靶点。在这篇文章中，我们报告了第一个 CD147 蛋白水解靶向嵌合体 (PROTAC) 的发现，该嵌合体源自天然产物伪月桂酸 B (PAB)。代表性化合物6a在体外和体内有效诱导 CD147 降解并抑制黑色素瘤细胞。6a可用作新型抗癌剂或用作分子生物学研究工具包的一部分，用于 CD147 在癌症网络中的动态作用的功能获得研究。