Unlocking thalidomide

Thalidomide has been used in humans since the 1950s, but the molecular mechanisms responsible for its known therapeutic and teratogenic effects are not well characterized. Researchers in Japan have now provided insight into the latter by showing that the developmental defects caused by thalidomide stem from the drug's ability to bind to cereblon.¹ The findings provide the first step toward a blueprint for developing new thalidomide analogs and derivatives with reduced risk of birth defects.

The Japanesegroup used bead-based affinity purification studies to show that thalidomide binds to cereblon (CRBN), whereas a nonteratogenic analog, phthalimide, does not. CRBN is a component of anE3 ubiquitin ligase complex, whichattaches ubiquitin molecules to their substrates to mark them for degradation...