Chemical Inhibitors of the Calcium Entry Channel TRPV6

Landowski, Christopher P.; Kopf, Katrin Annika; Suzuki, Yoshiro; Hediger, Matthias A. (2011). Chemical Inhibitors of the Calcium Entry Channel TRPV6 Pharmaceutical Research, 28(2), pp. 322-330. Springer 10.1007/s11095-010-0249-9

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PURPOSE: Calcium entry channels in the plasma membrane are thought to play a major role in maintaining cellular Ca(2+) 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 IC(50) value for growth inhibition by blocking endogenous Ca(2+) 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

School of Agricultural, Forest and Food Sciences HAFL > Consumer-focused Food Production

Name:

Landowski, Christopher P.;
Kopf, Katrin Annika0000-0002-7443-7489;
Suzuki, Yoshiro and
Hediger, Matthias A.

Subjects:

Q Science > QD Chemistry

ISSN:

0724-8741

Publisher:

Springer

Language:

English

Submitter:

Katrin Annika Kopf

Date Deposited:

18 Dec 2019 08:26

Last Modified:

18 Dec 2020 13:29

Publisher DOI:

10.1007/s11095-010-0249-9

ARBOR DOI:

10.24451/arbor.9250

URI:

https://arbor.bfh.ch/id/eprint/9250

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