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Chemical Inhibitors of the Calcium Entry Channel TRPV6

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Calcium entry channels in the plasma membrane are thought to play a major role in maintaining cellular Ca2+ levels, crucial for growth and survival of normal and cancer cells. The calcium-selective channel TRPV6 is expressed in prostate, breast, and other cancer cells. Its expression coincides with cancer progression, suggesting that it drives cancer cell growth. However, no specific inhibitors for TRPV6 have been identified thus far.


To develop specific TRPV6 inhibitors, we synthesized molecules based on the lead compound TH-1177, reported to inhibit calcium entry channels in prostate cancer cells in vitro and in vivo.


We found that one of our compounds (#03) selectively inhibited TRPV6 over five times better than TRPV5, whereas TH-1177 and the other synthesized compounds preferentially inhibited TRPV5. The IC50 value for growth inhibition by blocking endogenous Ca2+ entry channels in the LNCaP human prostate cancer cell line was 0.44 ± 0.07 μM compared to TH-1177 (50 ± 0.4 μM).


These results suggest that compound #03 is a relatively selective and potent inhibitor for TRPV6 and that it is an interesting lead compound for the treatment of prostate cancer and other cancers of epithelial origin.

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Ca2+ release-activated Ca2+


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nuclear factor of activated T-cells




calcium release-activated calcium channel protein 1




severe combined immunodeficiency


store-operated calcium channel


stromal interaction molecule 1




transient receptor potential


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This study was supported by the Swiss National Science Foundation (Hediger), Novartis Foundation (Hediger), NIH/NCI (Hediger), Marie Curie Reintegration Grant (Hediger) and Bernese Cancer League (Landowski). We thank Leah Witton for her helpful comments on the manuscript.

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Correspondence to Matthias A. Hediger.

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Landowski, C.P., Bolanz, K.A., Suzuki, Y. et al. Chemical Inhibitors of the Calcium Entry Channel TRPV6. Pharm Res 28, 322–330 (2011).

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