Cyclopamine and hedgehog signaling: chemistry, biology, medical perspectives.
نویسندگان
چکیده
When Odysseus left the devastated city of Troy after ten years of siege he could not foresee the perils he still had to face. The encounter with the cyclops, a giant with only one eye placed in the middle of its forehead, was doubtlessly one of the creepiest and most dangerous of his adventures. In the end, Odysseus could only escape with the help of a sheep. Whether Homers cyclops was inspired by the observation of terribly malformed neonates remains speculative. However, when sheep herders in Idaho in the middle of the 20th century faced an increasing number of cyclops-like sheep in their herds, a unique cascade of chemical, biological, and medicinal discoveries was initiated. This Minireview tells this story and shows its impact on modern biomedical research.
منابع مشابه
Roughing up Smoothened: chemical modulators of Hedgehog signaling
Small-molecule antagonists of Hedgehog-pathway signaling, such as cyclopamine, have been known for some time. Now, small-molecule agonists of the Hedgehog pathway have also been identified. The finding that both antagonists and agonists target the protein Smoothened supports the emerging hypothesis that Smoothened may be regulated by endogenous small molecules.
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BACKGROUND The Hedgehog signaling pathway is essential for embryogenesis and for tissue homeostasis in the adult. However, it may induce malignancies in a number of tissues when constitutively activated, and it may also have a role in other forms of normal and maladaptive growth. Cyclopamine, a naturally occurring steroidal alkaloid, specifically inhibits the Hedgehog pathway by binding directl...
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Stimulation of Hedgehog (Hh) signaling induces carcinogenesis or promotes cell survival in cancers of multiple organs. In epithelial cancer with aberrant Hedgehog activation, abrogation of Hedgehog signaling by cyclopamine, a naturally occurring Hedgehog-specific small-molecule inhibitor, causes profound inhibition of tumor growth. In the present study, cyclopamine displayed a significant poten...
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L ung cancer is the leading cause of cancer-related death worldwide nowadays. Non-small cell lung cancer (NSCLC) is relatively resistant to both chemotherapy and radiotherapy. 1 Sonic hedgehog (SHH) signaling pathway plays an important role in developmental biology, and recently, the activation of SHH signaling pathway has been reported to have a critical role in a subset of lung cancers. 2 Cyc...
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ورودعنوان ژورنال:
- Angewandte Chemie
دوره 49 20 شماره
صفحات -
تاریخ انتشار 2010