(-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels

  • Angew Chem Int Ed Engl. 2015 Mar 16;54(12):3787-91. doi: 10.1002/anie.201411511.
Yasemin Akbulut  1 ,  Hannah J Gaunt ,  Katsuhiko Muraki ,  Melanie J Ludlow ,  Mohamed S Amer ,  Alexander Bruns ,  Naveen S Vasudev ,  Lea Radtke ,  Matthieu Willot ,  Sven Hahn ,  Tobias Seitz ,  Slava Ziegler ,  Mathias Christmann ,  David J Beech ,  Herbert Waldmann
Affiliations
  • 1. Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany); Technische Universität Dortmund, Fakultät Chemie, Lehrbereich Chemische Biologie, Otto-Hahn-Strasse 6, 44227 Dortmund (Germany).
PMID: 25707820 DOI: 10.1002/anie.201411511
Abstract

Current therapies for common types of Cancer such as renal cell Cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal Cancer cells through activation of calcium-permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (-)-englerin A. This compound was found to be a highly efficient, fast-acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high-affinity extracellular (-)-englerin A binding site may open up novel opportunities for drug discovery aimed at renal Cancer.

Keywords
antitumor agents; calcium ions; ion channels; natural products.
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