133714-80-4Relevant articles and documents
Chemical inhibitors of the calcium entry channel TRPV6
Landowski, Christopher P.,Bolanz, Katrin A.,Suzuki, Yoshiro,Hediger, Matthias A.
experimental part, p. 322 - 330 (2012/03/10)
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 IC 50 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.
Design, synthesis, and biological evaluation of novel T-Type calcium channel antagonists
McCalmont, William F.,Heady, Tiffany N.,Patterson, Jaclyn R.,Lindenmuth, Michael A.,Haverstick, Doris M.,Gray, Lloyd S.,Macdonald, Timothy L.
, p. 3691 - 3695 (2007/10/03)
This paper describes the synthesis of several novel T-type calcium channel antagonists that inhibit calcium influx into the cell, which in turn regulates unknown aspects of the cell cycle pathway that are responsible for cellular proliferation. A library of compounds was synthesized anda brief structure activity relationship will be described. From these studies we have identified a compound (1) that displays anti-proliferative activity in the low micromolar range across a variety of cancer cell lines.
5,11-dihydrodibenzo[b,e][1,4]-thiazepines useful as gastro intestinal selective calcium antagonists
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, (2008/06/13)
The invention provides compounds of the formula: STR1 wherein k is 1, 2 or 3; m is 1, 2 or 3; n is 1, 2 or 3; p is 0, 1 or 2; X is O, S or a direct link, with the proviso that when X is O or S, n is 2 or 3; R1 is H or C1-C4 alkyl; and R2 is an optionally substituted phenyl or heteroaryl group; and pharmaceutically acceptable salts thereof. These compounds are useful for the treatment of motility disorders, particularly those of the gut such as irritable bowel syndrome.
