Discovery of novel photocaged ERK1/2 inhibitors as light-controlled anticancer agents

Abstract

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.