Chemical inhibitors of the calcium entry channel TRPV6

Christopher Landowski, Katrin A. Bolanz, Yoshiro Suzuki, Matthias A. Hediger*

*Corresponding author for this work

    Research output: Contribution to journalArticleScientificpeer-review

    48 Citations (Scopus)

    Abstract

    Purpose: 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.

    Methods: 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.

    Results: 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).

    Conclusions: 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.
    Original languageEnglish
    Pages (from-to)322-330
    JournalPharmaceutical Research
    Volume28
    Issue number2
    DOIs
    Publication statusPublished - 2011
    MoE publication typeA1 Journal article-refereed

    Keywords

    • breast cancer
    • calcium channel
    • chemical inhibitors
    • prostate cancer
    • TRPV6

    Fingerprint

    Dive into the research topics of 'Chemical inhibitors of the calcium entry channel TRPV6'. Together they form a unique fingerprint.

    Cite this