A looking glass perspective: thalidomide and cyclopamine.
Numerous naturally-occurring and synthetic compounds that were discovered initially because of their toxic properties, were later shown to possess biological activities beneficial to humans that enabled them to serve as templates 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 efficacy in treating several diseases has resulted in the recrudescence of the drug to society's usage. A current example of this phenomenon is the plant teratogen cyclopamine (11-deoxojervine), whose deleterious terata-inducing effects were restricted to grazing animals, but whose recently discovered inhibition of Sonic hedgehog signal transduction has provided both the potential to increase our understanding of organogenesis and to serve as a lead compound in drug development.
Gaffield
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Western Regional Research Center, ARS, USDA, Albany CA 94710, USA. wg@pw.usda.gov
Incardona
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Kapur
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Roelink
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D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001675:Bioethics; D053823:Hedgehog Proteins; D006801:Humans; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013723:Teratogens / Q000737:chemistry / Q000494:pharmacology*; D013792:Thalidomide / Q000737:chemistry / Q000494:pharmacology*; D015534:Trans-Activators; D014704:Veratrum Alkaloids / Q000737:chemistry / Q000494:pharmacology*
D053823:Hedgehog Proteins; D006993:Hypnotics and Sedatives; D011506:Proteins; C509239:SHH protein, human; D013723:Teratogens; D015534:Trans-Activators; D014704:Veratrum Alkaloids; D013792:Thalidomide; C000541:cyclopamine