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GENTAUR
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C-8700 Cyclopamine, >99%
[11-Deoxyjervine]
| M.W. 411.63 |
C27H41NO2 |
[4449-51-8]
RTECS GY0750000 |
SPECIAL HAZARD: TERATOGEN. Gloves and mask should be worn when
using this compound. Care must be taken to prevent contact through all
routes of exposure. Women of childbearing age should be extremely
careful in handling cyclopamine!
Storage: Store at or below -20 ºC. Solubility: See
below. Disposal: A
 | Cyclopamine blocks activation of the Hedgehog response pathway
associated with mutations that either activate the proto-oncogene Smoothened
(Smo) or inactivate the tumour suppressor Patched (Ptch) both of which
encode multipass transmembrane proteins. Furthermore, it has been
demonstrated that the inhibitory effect of cyclopamine results from its
direct binding to the Smo heptahelical protein bundle. Taipale, J., et
al. "Effects of oncogenic mutations in Smoothened and Patched can be
reversed by cyclopamine." Nature 406: 944-945 (2000). Chen,
J.K., et al. "Inhibition of Hedgehog signaling by direct binding of
cyclopamine to Smoothened." Genes & Dev. 16: 2743-2748
(2002) |
| Induces chick embryo malformations associated with the interruption of
Sonic hedgehog (Shh)-mediated dorsoventral patterning. Incardona, J.P.,
et al. "The teratogenic Veratrum alkaloid cyclopamine inhibits sonic
hedgehog signal transduction." Development. 125: 3553-3562
(1998). |
| Displays anti-tumor properties. It has been shown to induce apoptosis
in both colorectal adenoma- and carcinoma-derived cell lines and in skin
basal cell carcinomas. Qualtrough, D., et al. "Hedgehog signalling
in colorectal tumour cells: induction of apoptosis with cyclopamine
treatment." Int J Cancer. 110:831-837 (2004). Tabs, S., and
Avci, O. "Induction of the differentiation and apoptosis of tumor cells in
vivo with efficiency and selectivity." Eur J Dermatol. 14:
96-102 (2004). |
| Pregnant cattle, goats, or sheep who graze on the corn lily plant
(Veratrum californicum) at the 14th day of gestation can give birth to
deformed offspring with a characteristic single eye in the middle of the
forehead. [For example, view www.cybergoat.com/cyclopia/cyclopia.htm]
This type of birth defect recalls one of the most unforgettable images in
all of mythology, namely Homer's Cyclops (for which cyclopamine was named).
If plants containing cyclopamine or a similar compound existed in the
Mediterranean area in ancient times, it would then seem likely that the
Cyclops was not merely a product of Homer's imagination but rather was based
on known, naturally-occurring birth defects in animals. |
| CYCLOPAMINE SOLUBILITY: Ethanol is the best cyclopamine solvent
for biological use. A 2% solution (20 mg/mL) can be prepared by heating the
cyclopamine in ethanol with a heat gun; boiling is not necessary. Upon
cooling, the cyclopamine remains in solution at room temperature, even if
left for several days. However, storage at -20 ºC is recommended,
and at this temperature the cyclopamine will crystallize out of solution.
Upon thawing, the mixture will need to be heated again to redissolve the
cyclopamine. Methanol and DMSO can also be used as
cyclopamine solvents, but solubility in methanol is only about 0.7% (7
mg/mL) at best, and solubility in DMSO is about 0.4% (4 mg/mL). Substantial
heating is again needed to achieve solution with methanol or DMSO, but once
the cyclopamine is dissolved it will remain in solution if kept at room
temperature. Storage in either solvent at the recommended -20 ºC will also
cause crystallization, as noted above for ethanol, and reheating is
necessary after thawing in order to achieve full dissolution.
Methanol is less desirable than the other two solvents because it is the
most volatile; merely standing open in air will lead to slow volume loss and
consequent artefactual increase in concentration of the solution. DMSO is
the least volatile solvent and is preferred if a stock solution need only be
4 mg/mL or less. Ethanol is a compromise between volatility and achievable
concentration. |
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