 AKA:  Corn lily  False hellebore  Skunk cabbage  Family Liliaceae  Native to mountain meadows in the Sierra Nevadas and the Rockies

 Perennial monocot  Grows 1-2 meters tall  Stem/leaves resemble cornstalk

 Used by native Americans to treat wounds  Contraceptive  Root is an analgesic and disinfectant  Also used to treat VD

 Sheep herds were plagued by unexplained birth defects  Intensive study by the USDA isolated cyclopamine as the causative agent

 Required for tissue maintenance and regeneration  T-cell activation  Can act as a mitogen  Tissue dependent

 GPCRs (G Protein Coupled Receptor) are responsible for a multitude of signal cascades : 1. Adenylate cyclase/cAMP pathway  Activates PKA, which activates ion channels 2. Phospholipase C pathway  Secretion and translocation of proteins from the ER 3. IP 3 pathway:  Releases Ca+ from ER activating 4. Ca+/Calmodulin pathway 5. Glycogen pathway (via Adenylate cyclase)

 Phase I clinical trials underway of a derivate  GDC-0449 (Genentech in collaboration with Curis)  Preliminary results were promising  Side effects: loss of hair, weight loss, otherwise mild toxicity reported  Already being billed as “hav[ing] the potential to become a blockbuster drug…for treating cancers.” (Wong, 2009)

 Glioblastoma multiforme (brain tumor)  2-3 cases per 100K  Most often terminal  Median survival = 15 months (conventional chemotherapy)  Without treatment = 4.5 months (World Heath Organization)

 Synthetic drug marketed as a sedative  Prescribed to pregnant women to help with morning sickness  Drug testing conducted on rats  Rats metabolized thalidomide  Late 1950’s children born with Pharcomelia  Later tests on monkeys produced same birth defects as seen in humans

 Berry, L. (n.d.). Sierra Wild Flowers. Retrieved Oct 23, 2009, from Sierrawildflowers.org:  Binns, W. L. (1968). Effects of Teratogenic Agents in Range Plants. Cancer Research, 28,  Keeley. (2002). Biology News. Retrieved Oct 23, 2009, from Bio- Medicine: compound-kills-brain-tumor-cells /  Lingham, A. (2000, June). The First Appearance of Thalidomide. Retrieved Oct 23, 2009, from Thalidomide Isomerism and Optical Isomerism:  Wong, J. F. (2009). Genetic Engineering & Biotechnology News. Retrieved Oct 23, 2009, from GEN: hid=4