Identification of a Primary Target of Thalidomide Teratogenicity

Thalidomide Teratogenicity Target

In the late 1950s and early 1960s, thalidomide was prescribed to pregnant women as a cure for morning sickness, but it was then found to have developmental defects, most obviously, stunted limbs in thousands of babies. Although its use was banned worldwide, thalidomide has since been found to be a valuable treatment for a range of cancers, inflammatory disorders, and leprosy. Several hypotheses have been proposed, but the mechanism of action of thalidomide is unknown. Using zebrafish and chicken as animal models, Ito et al. (p. 1345 ) show that the protein cereblon is a primary target of thalidomide. Thalidomide exerts teratogenic effects by binding to cereblon and inhibiting associated enzymatic activity important for limb development. Knowing the mechanism of action of thalidomide should encourage the search for thalidomide derivatives without teratogenic activity.