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, E-diazo stereoisomer (Z/E = 3:97, IC₅₀ ≫ 10 μM) and a potent inhibitor as the Z-diazo stereoisomer accessible reversibly by UV irradiation at λ = 365 nm (Z/E = 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.

SUBMITTER: Cunha MR 

PROVIDER: S-EPMC6746075 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature