Cyclopamine

A natural steroidal alkaloid that inhibits hedgehog (Hh) signaling with IC50 of 46 nM; inhibits hedgehog-dependent expression of Pax7 with IC50 of 24 nM, blocks the response of neural plate explants to recombinant Shh-N; A useful tool in studying the role of Hh in normal development, and as a potential treatment for certain cancers in which Hh is overexpressed.(In Vitro):Treatment with small molecule Hh inhibitors such as HhAntag and the natural product Cyclopamine, both binding to Smo, induces tumor remission in a genetic mouse model of medulloblastoma. Cyclopamine is a Hedgehog (Hh) pathway antagonist. Cyclopamine suppresses cell growth. Cyclopamine (3 μM) suppression of Hh pathway activity and growth in digestive tract tumour cell lines correlates with expression of PTCHmRNA. Cyclopamine is a steroidal alkaloid that inhibits Hh signalling through direct interaction with Smo.(In Vivo):Cyclopamine causes durable regression of xenograft tumors. Tumors in Cyclopamine-treated animals, regress completely by 12 days. Cyclopamine (1.2 mg) treatment blocks tumour formation of human pancreatic adenocarcinoma cells after transplantation into nude mice.