Zhu Tian-Yu, Wu Xiu-Tao, Chen Chen, Liu Xiao-Qin, Zhu Li, Luo Jian-Guang, Kong Ling-Yi
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
ACS Med Chem Lett. 2022 Feb 2;13(3):449-456. doi: 10.1021/acsmedchemlett.1c00625. eCollection 2022 Mar 10.
Harringtonolide (, ) is a bioactive diterpenoid tropone isolated from with antiproliferation activity. Until now there have been no reports to elucidate its anticancer mechanism. Herein we report the synthesis of -derived probes (, , and ) to identify the possible target of . As a result, the application of a novel photoaffinity alkyne-tagged probe from (compound ) showed direct engagement between and receptor for activated C kinase 1 (RACK1). Furthermore, could suppress the epithelial-mesenchymal transition (EMT) process and inhibit activation of the FAK/Src/STAT3 signaling pathway in A375 cells. This study provides a groundwork for as an effective antitumor agent that targets RACK1 to suppress cancer cell migration.
哈林顿醇内酯（，）是一种从[来源未提及]中分离得到的具有生物活性的二萜类环庚三烯酚酮，具有抗增殖活性。迄今为止，尚无报道阐明其抗癌机制。在此，我们报道了[未提及具体物质名称]衍生探针（，和）的合成，以确定[未提及具体物质名称]的可能靶点。结果，一种新型的来自[未提及具体物质名称]的光亲和炔烃标记探针（化合物）的应用表明，[未提及具体物质名称]与活化C激酶1受体（RACK1）之间存在直接相互作用。此外，[未提及具体物质名称]可抑制A375细胞中的上皮-间质转化（EMT）过程，并抑制FAK/Src/STAT3信号通路的激活。本研究为[未提及具体物质名称]作为一种靶向RACK1以抑制癌细胞迁移的有效抗肿瘤药物奠定了基础。
