(−)‐Englerin A is a Potent and Selective Activator of TRPC4 and TRPC5 Calcium Channels1. Issue 12 (23rd February 2015)

• Record Type: Journal Article
• Authors: Akbulut, Yasemin; Gaunt, Hannah J.; Muraki, Katsuhiko; Ludlow, Melanie J.; Amer, Mohamed S.; Bruns, Alexander; Vasudev, Naveen S.; Radtke, Lea; Willot, Matthieu; Hahn, Sven; Seitz, Tobias; Ziegler, Slava; Christmann, Mathias; Beech, David J.; Waldmann, Herbert
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 12(2015)
• Page Start: 3787
• Page End: 3791
• Publication Date: 2015-02-23
• Subjects: antitumor agents -- calcium ions -- ion channels -- natural products; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201411511
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Natural born killer : The sesquiterpene (−)‐englerin A rapidly and selectively kills renal cancer cells through activation of calcium‐permeable nonselective transient receptor potential canonical (TRPC) calcium channels. It is a highly efficient, fast‐acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels (PM=plasma membrane).