Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 64, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2022.128683
Keywords
Photoinduced drug release; Photocaged B-Raf V600E inhibitor; Melanoma; Precise treatment
Categories
Funding
- National Natural Science Foundation of China [22037003, 81820108029, 81874284]
- State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry
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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.
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.
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