Chen Rui, Wang Ziyue, Liu Lihong, Pan Zhengying
State Key Laboratory of Chemical Oncogenomics, Provincial Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University Xili University Town, PKU Campus, F-311, Shenzhen, 518055, China.
Chem Commun (Camb). 2022 Apr 14;58(31):4901-4904. doi: 10.1039/d2cc00456a.
Although extracellular regulated protein kinases (ERKs) are considered important targets for the treatment of various cancers, the occurrence of severe side effects in clinical trials restricts the development of ERK inhibitors. Here, we developed the first series of photocaged ERK inhibitors, which can be selectively activated by UV irradiation to release a highly potent ERK inhibitor in multiple cancer cell lines including A375, A549 and HCT116, and Compound 2 demonstrated clear anticancer activity in a zebrafish xenograft model. In conclusion, photocaged ERK inhibitor 2 provides a new strategy for precise cancer therapy.
尽管细胞外调节蛋白激酶（ERKs）被认为是治疗各种癌症的重要靶点，但临床试验中严重副作用的出现限制了ERK抑制剂的开发。在此，我们开发了首个光笼化ERK抑制剂系列，其可通过紫外线照射选择性激活，在包括A375、A549和HCT116在内的多种癌细胞系中释放出高效的ERK抑制剂，并且化合物2在斑马鱼异种移植模型中表现出明显的抗癌活性。总之，光笼化ERK抑制剂2为精准癌症治疗提供了一种新策略。
