(-)-Englerin A is a Potent and Selective Activator of TRPC4 and TRPC5 Calcium Channels

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2015 Feb 25

PMID 25707820

Citations 98

Authors

Yasemin Akbulut

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

Soon will be listed here.

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.

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