Open AccessPhotoswitchable Inhibitor of the Calcium Channel TRPV6
Author(s) -
Micael Rodrigues Cunha,
Rajesh Bhardwaj,
Sonja Lindinger,
Carmen Butorac,
Christoph Romanin,
Matthias A. Hediger,
JeanLouis Reymond
Publication year - 2019
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00298
Subject(s) - trpv6 , calcium channel , transient receptor potential channel , calcium , diazo , chemistry , ic50 , transporter , pharmacology , medicine , in vitro , biochemistry , receptor , gene , medicinal chemistry , organic chemistry
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, IC 50 ≫ 10 μM) and a potent inhibitor as the Z -diazo stereoisomer accessible reversibly by UV irradiation at λ = 365 nm ( Z/E = 3:1, IC 50 = 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.