Molecule of the Moment: Cyclopamine

creative commons (sheep: By Kreuzschnabel; corn lily: DcRjSr)

creative commons (sheep: By Kreuzschnabel; corn lily: DcRjSr)

cyclopamine

cyclopamine

Name: cyclopamine

Source: corn lily (Veratrum californicum)

Chemical structure: steroidal alkaloid (in other words, steroid-based molecule containing a nitrogen)

upsetting image of a cyclops lamb (via USDA-Agricultural research services)

upsetting image of a cyclops lamb (via USDA-Agricultural research services)

Discovery:  The search for cyclopamine began in 1957 after the birth of a one-eyed sheep on a farm in Idaho.  Unfortunately this was not an isolated incident, and once several more cyclops lambs emerged, scientists set out to uncover the causative agent behind this striking birth defect.  It took 11 years (involving multiple summers of literally living with the sheep) for researchers, led by Lynn James, to pinpoint corn lilies as the culprit.  By closely observing sheep behavior, James realized that during times of drought the herd would move to higher ground and graze on the flowers and roots of the innocuous-seeming corn lily.  It took several more years for chemists to determine that the cyclopia-inducing agent was a small molecule, which they, appropriately, dubbed cyclopamine.  

Biology: Cyclopamine blocks a protein involved in the hedgehog signaling pathway (named after Sonic the hedgehog - for real).  This pathway is involved in numerous processes related to development and cancer.  Before researchers uncovered the relationship between cyclopamine and hedgehog, mutations in proteins along this pathway were implicated in developmental malformations. 

Odysseus and his guys kill the cyclops polyphemus, eleusis museum (via napoleon vier from nl)

Odysseus and his guys kill the cyclops polyphemus, eleusis museum (via napoleon vier from nl)

Uses: It turns out that in multiple types of cancer, components of the hedgehog pathway are over-expressed - or hyperactive.  Since cyclopamine is known to block this pathway, several pharmaceutical companies have worked towards developing this molecule (or derivatives) as an anti-cancer therapeutic.  As of yet nothing notable has emerged.  

Dangers:  This seems obvious, but do not ingest this molecule if pregnant.  It causes severe birth defects.  

Fact that can be used to impress friends/foes at a cocktail party:  

Cyclopamine is a molecule that recalls one of the best scenes from The Odyssey.  It has an awesome name, a cool history, and potential as an anti-cancer agent.  

-AMC