A novel photocaged B-RafV600E inhibitor toward precise melanoma treatment

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-Raf(V600E) inhibitor 1. Accordingly, once activated by the UV light, compound 2 could potently inhibit the proliferation of melanoma cells bearing B-Raf(V600E) 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.

Automated summary

Photoinduced drug release is a promising strategy for precise cancer therapy. The newly designed photocaged B-RafV600E inhibitor 2 can release active drugs under UV irradiation, effectively inhibiting the proliferation of melanoma cells and showing similar effects under sunlight exposure.