Photoswitchable Inhibitor of the Calcium Channel TRPV6

Abstract

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, <i>E</i>-diazo stereoisomer (<i>Z/E</i> = 3:97, IC₅₀ ≫ 10 μM) and a potent inhibitor as the <i>Z</i>-diazo stereoisomer accessible reversibly by UV irradiation at λ = 365 nm (<i>Z/E</i> = 3:1, IC₅₀ = 1.7 ± 0.4 μM), thereby allowing precise spatiotemporal control of inhibition. This new tool compound should be useful to deepen our understanding of TRPV6.