Molecule of the Month
April 2013
Calcium Channel 115Blockers

Intracellular Ca2+ concentrations, among many other things, also influence cell proliferation. TRPV6 is a highly selective Ca2+ channel which is mainly responsible for Ca2+ uptake in the small intestine, but it is also found in placenta, pancreas and the prostate. Given that TRPV6 is overexpressed in prostate cancer, as well as in other cancers, we have developed diarylborinate inhibitors against this target. The borinate depicted inhibited TRPV6 in the low micromolar range and showed selectivity over store-operated calcium channels.

This work was carried out in the groups of Prof. Martin Lochner (DCB) and Prof. Matthias A. Hediger (Institute of Biochemistry and Molecular Medicine) and is part of an NCCR TransCure project.

References:

  • A. Hofer, G. Kovacs, A. Zappatini, M. Leuenberger, M. A. Hediger, M. Lochner;
    "Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport"
    Bioorg. Med. Chem., 21, 32023213, (2013); doi:10.1016/j.bmc.2013.03.037.
  • G. Kovacs, N. Montalbetti, A. Simonin, T. Danko, B. Balazs, A. Zsembery, M. A. Hediger;
    "Inhibition of the human epithelial calcium channel TRPV6 by 2-aminoethoxydiphenyl borate (2-APB)"
    Cell Calcium, 52, 468-480, (2012); doi:10.1016/j.ceca.2012.08.005.