Reymond Research Group

University of Bern

Photoswitchable Inhibitor of the Calcium Channel TRPV6

The paper Photoswitchable Inhibitor of the Calcium Channel TRPV6 has been published by ACS Medicinal Chemistry Letters.

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.

Author(s): Micael R. Cunha, Rajesh Bhardwaj, Sonja Lindinger, Carmen Butorac, Christoph Romanin, Matthias A. Hediger and Jean-Louis Reymond