Cyclopamine, a Naturally Occurring Alkaloid, and Its Analogues May Find Wide Applications in Cancer Therapy

Cyclopamine is a naturally occurring steroidal alkaloid that attenuates the Hedgehog signaling pathway by inhibiting the Smoothened receptor. The Hedgehog pathway plays an important role in many human cancers. Cyclopamine has served as a pivotal tool compound in elucidating the pharmacological effect of the Hedgehog signaling pathway, however, due to its poor solubility, stability, and moderate activity, its clinical development has been impeded. Significant efforts were made to overcome the shortcomings of cyclopamine, giving which results cultivated in the identification of IPI- 926, a derivative of cyclopamine, which proceeded to clinical trials.