Chemical inhibitors of the calcium entry channel TRPV6

Pharm Res. 2011 Feb;28(2):322-30. doi: 10.1007/s11095-010-0249-9. Epub 2010 Nov 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Calcium / metabolism*
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Econazole / analogs & derivatives
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Miconazole / analogs & derivatives
  • Prostatic Neoplasms / metabolism
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology*
  • RNA, Small Interfering / pharmacology
  • TRPV Cation Channels / antagonists & inhibitors*


  • Calcium Channel Blockers
  • Calcium Channels
  • Pyrrolidines
  • RNA, Small Interfering
  • TH 1177
  • TRPV Cation Channels
  • TRPV5 protein, human
  • TRPV6 protein, human
  • Econazole
  • Miconazole
  • Calcium