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

被引：156

作者：

Akbulut, Yasemin ^{[1
,2
]}

Gaunt, Hannah J. ^{[3
]}

Muraki, Katsuhiko ^{[4
]}

Ludlow, Melanie J. ^{[3
]}

Amer, Mohamed S. ^{[3
,5
]}

Bruns, Alexander ^{[3
]}

Vasudev, Naveen S. ^{[3
]}

Radtke, Lea ^{[6
]}

Willot, Matthieu ^{[6
]}

Hahn, Sven ^{[6
]}

Seitz, Tobias ^{[6
]}

Ziegler, Slava ^{[1
]}

Christmann, Mathias ^{[6
]}

Beech, David J. ^{[3
]}

Waldmann, Herbert ^{[1
,2
]}

机构：

[1] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany

[2] Tech Univ Dortmund, Fak Chem, Lehrbereich Chem Biol, D-44227 Dortmund, Germany

[3] Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England

[4] Aichi Gakuin Univ, Sch Pharm, Chikusa Ku, Nagoya, Aichi 4648650, Japan

[5] Menoufiya Univ, Dept Clin Physiol, Fac Med, Al Minufya, Egypt

[6] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2015年 / 54卷 / 12期

基金：

欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

antitumor agents; calcium ions; ion channels; natural products; BIOLOGY-ORIENTED SYNTHESIS; NATURAL-PRODUCTS; ENGLERIN; DISCOVERY;

D O I：

10.1002/anie.201411511

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：3787 / 3791

页数：5

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