Discovery of a novel photoswitchable PI3K inhibitor toward optically-controlled anticancer activity.

Light has been used increasingly as an external stimulus in drug design. Herein, we report a novel photoswitchable azo-PI3K inhibitor, which bears an azobenzene moiety and can be efficiently converted between trans and cis configuration with changes of anticancer activity upon different light irradiation. Its photochemical properties were characterized by UV, LC-MS and NMR techniques. In biological assessment, trans and cis isomers of the azo-PI3K inhibitor exhibited differential anticancer activity in inhibition of PI3K pathway, cell migratory ability, and colony formation and can be switched at a cellular level upon light irradiation. Moreover, both isomers of the azo-PI3K inhibitor significantly inhibited tumor growth in a zebrafish xenograft model. Together, this photoswitchable azo-PI3K inhibitor may be useful as a valuable tool compound for studying the PI3K pathway and further optimization toward optically-controlled anticancer activity.