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ID: ALA5120796

Journal: Bioorg Med Chem Lett

Title: A novel photocaged B-RafV600E inhibitor toward precise melanoma treatment.

Authors: Chen Z, Ke R, Song Z, Zhou Y, Ren X, Huang W, Wang Z, Ding K.

Abstract: Photoinduced drug release can reduce systemic side effects by releasing active drugs with high spatiotemporal accuracy, representing a promising strategy for precise cancer therapy. Here we designed and synthesized a novel photocaged B-RafV600E inhibitor 2, which, upon UV irradiation, could release a potent B-RafV600E inhibitor 1. Accordingly, once activated by the UV light, compound 2 could potently inhibit the proliferation of melanoma cells bearing B-RafV600E mutant while sparing melanoma cells expressing wild-type B-Raf, and could dose-dependently suppress the activation of the MAPK signaling pathway. Notably, the UV-mediated active component release and the resulting antiproliferative effects of compound 2 could be recapitulated when exposed to the sunlight, greatly enhancing its practicality. This photocaged B-RafV600E inhibitor 2 might serve as a novel therapeutic agent toward precise melanoma treatment.

CiteXplore: 35307569

DOI: 10.1016/j.bmcl.2022.128683