Issue 5, 2016

I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs

Abstract

Covering: 1950s to 2015

During the 1950s, sheep ranchers in the western United States experienced episodic outbreaks of cyclopic lambs. In this highlight I describe how these mysterious incidents were traced to the grazing of Veratrum californicum wildflowers by pregnant ewes, leading to the discovery of cyclopamine (1) as a plant-derived teratogen. The precise mechanism of cyclopamine action remained enigmatic for 30 years, until this steroid alkaloid was found to be the first specific inhibitor of Hedgehog (Hh) signalling and a direct antagonist of the transmembrane receptor Smoothened (SMO). In addition to being a valuable probe of Hh pathway function, cyclopamine has been used to demonstrate the therapeutic potential of Hh pathway inhibitors. I discuss the development of SMO antagonists as anticancer therapies and emerging challenges.

Graphical abstract: I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs

Article information

Article type
Highlight
Submitted
08 dek 2015
First published
20 yan 2016

Nat. Prod. Rep., 2016,33, 595-601

Author version available

I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs

J. K. Chen, Nat. Prod. Rep., 2016, 33, 595 DOI: 10.1039/C5NP00153F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements