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(−)‐Englerin A is a Potent and Selective Activator of TRPC4 and TRPC5 Calcium Channels
Author(s) -
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
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201411511
Subject(s) - trpc , trpc5 , transient receptor potential channel , activator (genetics) , chemistry , calcium , extracellular , cancer research , pharmacology , receptor , biochemistry , medicine , organic chemistry
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.