A looking glass perspective: Thalidomide and cyclopamine

Numerous naturally-occurring and synthetic compounds that were discovered i nitially because of their toxic properties, were later shown to possess bio logical activities beneficial to humans that enabled them to serve as templ ates for the development of useful medicinal agents. A prominent example is thalidomide, a synthetic drug that gained notoriety originally due to its catastrophic teratogenicity in humans. The discovery of thalidomide's effic acy in treating several diseases has resulted in the recrudescence of the d rug to society's usage. A current example of this phenomenon is the plant t eratogen cyclopamine (11-deoxojervine), whose deleterious terata-inducing e ffects were restricted to grazing animals, but whose recently discovered in hibition of Sonic hedgehog signal transduction has provided both the potent ial to increase our understanding of organogenesis and to serve as a lead c ompound in drug development.