Cyclopamine

Cyclopamine
IUPAC name	(3β,​23R)-​17,​23-​epoxyveratraman-​3-​ol
Other names	11-deoxojervine (2'R,​3S,​3'R,​3'aS,​6'S,​6aS,​6bS,​7'aR,​11aS,​11bR)-​1,​2,​3,​3'a,​4,​4',​5',​6,​6',​6a,​6b,​7,​7',​7'a,​8,​11,​11a,​11b-​octadecahydro-​3',​6',​10,​11b-​tetramethyl-​spiro​[9H-​benzo​[a]​fluorene-​9,​2'(3'H)-​furo​[3,2-b]​pyridin]-​3-​ol
Identifiers
CAS number	4449-51-8
PubChem	442972
SMILES	C[C@H]1C[C@@H]2[C@H]([C@H]([C@]3(O2)CC[C@H]4[C@@H]5CC=C6C[C@H](CC[C@@]6([C@H]5CC4=C3C)C)O)C)NC1
Properties
Molecular formula	C27H41NO2
Molar mass	411.62 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Cyclopamine (11-deoxojervine) is a naturally-occurring chemical that belongs to the group of steroidal jerveratrum alkaloids. It is a teratogen isolated from the corn lily (Veratrum californicum) that can lead to cyclopia (holoprosencephaly).

Cyclopamine was named for one-eyed lambs which were born to sheep which grazed on wild corn lily at a farm in Idaho. In 1957 the US Department of Agriculture started an eleven-year investigation which led to the identification of cyclopamine as the cause of the birth defect.^[1]

Physiological effects

Cyclopamine inhibits the hedgehog signaling pathway (Hh) by influencing the balance between the active and inactive forms of the Smoothened protein.

Medical potential

Cyclopamine is currently being investigated as a treatment agent in basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma, tumors that result from excessive Hh activity ^[2], glioblastoma, and as a treatment agent for multiple myeloma.

Studies suggest that cyclopamine acts as a primary inhibitor of the so-called "hedgehog" signal-transduction pathway in cells. This pathway named for the ligand for the signal protein, is used by cells to help them react to external chemical signals. The pathway carries out important functions in embryonic development and when it goes awry, deformities can occur. However, errant activation of the pathway can also trigger cancer in adult humans, leading to basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, and prostate, pancreatic and breast cancers. A way of controlling the pathway using cyclopamine could turn this problem on its head and provide a way to treat cancer. Many anticancer drugs are paradoxically carcinogenic in healthy individuals^[3].

Notes

References

• Tas,S.,Avci , O., Induction of the differentiation and apotosis of tumor cells in vivo with efficiency and selectivity, Eur. J. Dermatology , 14: 96-102, 2004.
• Tas,S.,Avci , O.,Rapid Clearance of Psoriatic Skin Lesions Induced by Topical Cyclopamine, Dermatology, Vol.209,No:2, 2004.
• Garrossian, M. et al. "Synthesis and Anticancer Activity Studies of Cyclopamine Derivatives." Bioorganic & Medicinal Chemistry Letters 18 (2008): 1359-1363.

External links

• Cancer Drug Behind Cyclops Birth? (Wired News Article)
• Experimental Anti-cancer Drug Kills Brain Tumor Stem Cells (Science Daily)