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ACS Med Chem Lett. 2019 Aug 2;10(9):1341-1345. doi: 10.1021/acsmedchemlett.9b00298. eCollection 2019 Sep 12.

Photoswitchable Inhibitor of the Calcium Channel TRPV6.

Author information

1
Department of Chemistry and Biochemistry, NCCR TransCure, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
2
Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland & Department of Nephrology and Hypertension, University Hospital Bern, Inselspital, 3010 Bern, Switzerland.
3
Institute of Biophysics, Johannes Kepler University Linz, Gruberstrasse 40, 4020 Linz, Austria.

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.

PMID:
31531207
PMCID:
PMC6746075
[Available on 2020-09-12]
DOI:
10.1021/acsmedchemlett.9b00298

Conflict of interest statement

The authors declare no competing financial interest.

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