Cyclopamine (Aladdin C125994 ≥99%,  C276580 ethanol solution) is a steroidal alkaloid isolated from the corn lily (Veratrum californicum) and is best known for its ability to inhibit Hedgehog (Hh) signaling. Studies have shown that cyclopamine displays multiple biological effects, including anticancer and anti-inflammatory activities.

The Hedgehog pathway regulates cellular growth and differentiation, playing an essential role in embryonic development and tissue repair. In this pathway, Hh proteins bind to and inhibit the Patched receptor, which in turn permits accumulation of the transmembrane receptor Smoothened (Smo). Activated Smo prevents the cleavage (inactivation) of downstream transcription factors, ultimately leading to gene expression. Hyperactivation of Hh signaling has been associated with various cancers, as it can allow uncontrolled cell proliferation.

Inhibition of Hh signaling proteins has shown therapeutic promise in preclinical cancer studies. Mutations in Patched or Smo can result in constitutive pathway activation. Gain-of-function mutations in Smo, for example, enable signaling and gene transcription even without upstream input, and such mutations are strongly linked to basal cell carcinoma and colorectal cancer.

Cyclopamine directly targets and inhibits Smo, blocking Hh-mediated transcriptional activation. In colorectal cancer models, cyclopamine induces apoptosis in adenoma and carcinoma cells. In cholangiocarcinoma cell models, it prevents epithelial-to-mesenchymal transition, suppresses cell migration, invasion, and proliferation, and in animal models, it promotes tumor necrosis while reducing tumor growth.

Beyond oncology, cyclopamine has demonstrated additional protective effects. In animal models of cholestasis caused by hepatic ischemia/reperfusion injury, treatment with cyclopamine reduced activation of Akt and ERK signaling, lowered neutrophil infiltration, decreased pro-inflammatory cytokines and fibrosis biomarkers, and alleviated histological damage. In separate kidney fibrosis models, cyclopamine reduced fibronectin and collagen I expression, thereby preventing interstitial fibrosis following obstructive injury. 

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