Photoinduced Conversion of Antimelanoma Agent Dabrafenib to a Novel Fluorescent BRAF V600E Inhibitor.

Dabrafenib (Tafinlar) was approved in 2013 by the FDA as a selective single agent treatment for patients with BRAF mutation-positive advanced melanoma. One year later, a combination of dabrafenib and trametinib was used for treatment of BRAF mutant metastatic melanoma. In the present study, we report on hitherto not described photosensitivity of dabrafenib both in organic and aqueous media. The half-lives for dabrafenib degradation were determined. Moreover, we revealed photoinduced chemical conversion of dabrafenib to its planar fluorescent derivative dabrafenib_photo . This novel compound could be isolated and biologically characterized . Both enzymatic and cellular assays proved that is still a potent BRAF inhibitor. The intracellular formation of from dabrafenib upon ultraviolet irradiation is shown. The herein presented findings should be taken in account when handling dabrafenib both in preclinical research and in clinical applications.