Photoswitchable Inhibitor of the Calcium Channel TRPV6

摘要

Herein we report the first photoswitchable inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6), a selective calcium channel involved in a number of diseases and in cancer progression. By surveying analogs of a previously reported TRPV6 inhibitor appended with a phenyl-diazo group, we identified a compound switching between a weak TRPV6 inhibitor in its dark, E-diazo stereoisomer (Z/E = 3:97, IC50 10 mu M) and a potent inhibitor as the Z-diazo stereoisomer accessible reversibly by UV irradiation at lambda = 365 nm (Z/E = 3:1, IC50 = 1.7 +/- 0.4 mu M), thereby allowing precise spatiotemporal control of inhibition. This new tool compound should be useful to deepen our understanding of TRPV6.