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Updated: Jan 19, 2026
Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
Published on: December 13, 2024
Photoswitchable Inhibitor of the Calcium Channel TRPV6
Micael R Cunha1, Rajesh Bhardwaj2, Sonja Lindinger3
1Department of Chemistry and Biochemistry, NCCR TransCure, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
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.
Insights
Researchers developed the first photoswitchable inhibitor for Transient Receptor Potential Vanilloid 6 (TRPV6) calcium channels. This novel compound allows precise control over TRPV6 activity using light, aiding disease and cancer research.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Transient Receptor Potential Vanilloid 6 (TRPV6) is a selective calcium channel implicated in various diseases, including cancer progression.
- Controlling TRPV6 activity is crucial for understanding its role in physiological and pathological processes.
Purpose of the Study:
- To develop the first photoswitchable inhibitor for TRPV6.
- To enable precise spatiotemporal control over TRPV6 channel activity.
Main Methods:
- Synthesis and screening of TRPV6 inhibitor analogs featuring a phenyl-diazo group.
- Characterization of photoswitching behavior between E-diazo and Z-diazo stereoisomers using UV irradiation.
- Determination of inhibitory potency (IC50) for both stereoisomers.
Main Results:
- A novel photoswitchable TRPV6 inhibitor was identified.
- The dark-state E-diazo isomer showed weak inhibition (IC50 >> 10 μM).
- UV irradiation (365 nm) converted the inhibitor to the potent Z-diazo isomer (IC50 = 1.7 ± 0.4 μM) with reversible switching.
Conclusions:
- The developed photoswitchable inhibitor offers precise spatiotemporal control over TRPV6 activity.
- This tool compound is valuable for further research into TRPV6 function in diseases and cancer.
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