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Literature DB >> 25707820

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

Yasemin Akbulut¹, 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.

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.

Entities: Chemical

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

Mesh：

Substances：

Year: 2015 PMID： 25707820 PMCID： PMC7116557 DOI： 10.1002/anie.201411511

Source DB: PubMed Journal: Angew Chem Int Ed Engl ISSN： 1433-7851 Impact factor: 15.336

31 in total

1. Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5.

Authors: M Schaefer; T D Plant; A G Obukhov; T Hofmann; T Gudermann; G Schultz
Journal: J Biol Chem Date: 2000-06-09 Impact factor: 5.157

Review 2. Chemical synthesis of the englerins.

Authors: Rebecca H Pouwer; Jean-Alexandre Richard; Chih-Chung Tseng; David Y-K Chen
Journal: Chem Asian J Date: 2011-12-08

Review 3. The evolving role of natural products in drug discovery.

Authors: Frank E Koehn; Guy T Carter
Journal: Nat Rev Drug Discov Date: 2005-03 Impact factor: 84.694

Review 4. Biology-inspired synthesis of compound libraries.

Authors: M Kaiser; S Wetzel; K Kumar; H Waldmann
Journal: Cell Mol Life Sci Date: 2008-04 Impact factor: 9.261

Review 5. TRPs in our senses.

Authors: Nils Damann; Thomas Voets; Bernd Nilius
Journal: Curr Biol Date: 2008-09-23 Impact factor: 10.834

6. Total synthesis and biological evaluation of (-)-englerin A and B: synthesis of analogues with improved activity profile.

Authors: Lea Radtke; Matthieu Willot; Hongyan Sun; Slava Ziegler; Stephanie Sauerland; Carsten Strohmann; Roland Fröhlich; Peter Habenberger; Herbert Waldmann; Mathias Christmann
Journal: Angew Chem Int Ed Engl Date: 2011-03-29 Impact factor: 15.336

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

1. Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5.

Review 2. Chemical synthesis of the englerins.

Review 3. The evolving role of natural products in drug discovery.

Review 4. Biology-inspired synthesis of compound libraries.

Review 5. TRPs in our senses.

6. Total synthesis and biological evaluation of (-)-englerin A and B: synthesis of analogues with improved activity profile.

7. Corrigendum to "The Epidemiology of Renal Cell Carcinoma" [Eur Urol 2011;60:615-21].

8. A brief synthesis of (-)-englerin A.

9. Transient potential receptor channel 4 controls thrombospondin-1 secretion and angiogenesis in renal cell carcinoma.

Review 10. Renal cancer biomarkers: the promise of personalized care.

Review 1. Natural products as probes in pharmaceutical research.

2. Triple-negative breast cancer cell line sensitivity to englerin A identifies a new, targetable subtype.

Review 3. Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling.

Review 4. Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.

5. Pico145 - powerful new tool for TRPC1/4/5 channels.

Review 6. Charting a TRP to Novel Therapeutic Destinations for Kidney Diseases.

7. Critical roles of Gi/o proteins and phospholipase C-δ1 in the activation of receptor-operated TRPC4 channels.

8. Development of a carbon-11 PET radiotracer for imaging TRPC5 in the brain.

Review 9. TRPC channels: Structure, function, regulation and recent advances in small molecular probes.

10. Regulator of G-protein signalling and GoLoco proteins suppress TRPC4 channel function via acting at Gαi/o.