cyclopamine

**Cyclopamine** is a naturally occurring steroidal alkaloid isolated from the corn lily (Veratrum californicum)[1][3][7]. It is a potent, selective antagonist of the Hedgehog (Hh) signaling pathway, acting by binding to and inhibiting the twelve-transmembrane protein Smoothened (SMO)[1][5]. Cyclopamine's inhibition of the Hh pathway leads to downregulation of GLI transcription factors, subsequently repressing genes involved in cell proliferation, extracellular matrix (ECM) formation, and tumorigenesis[1][5][6]. Cyclopamine is teratogenic and was originally discovered due to its ability to cause severe birth defects in livestock. Though never developed into a marketed clinical therapy due to poor solubility, acid lability, manufacturing cost, toxicity, and side effects, cyclopamine has played a key foundational role in cancer research, particularly for tumors with aberrant Sonic Hedgehog (SHH) pathway activation such as basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, glioblastoma, multiple myeloma, breast cancer, colorectal cancer, pancreatic cancer, and esophageal carcinoma[3][4][5][6][7]. Cyclopamine suppresses tumor growth, proliferation, and invasion, induces cell cycle arrest (G1 phase), and promotes apoptosis—sometimes through direct toxic effects unrelated to Hh inhibition[2][5][6][7]. Its molecular scaffold inspired the development of clinically useful Hh pathway inhibitors (e.g., vismodegib, sonidegib)[3][4].

Other names

cyclopamine11-deoxojervine