Isolation of Cereblon CRBN Using Thalidomide

Lessons from Isolation of Cereblon (CRBN) Using Thalidomide 

To purify thalidomide-binding proteins, Handa and coworkers used covalent conjugation of a thalidomide derivative to a magnetic version of low-adsorption 

Human CRBN encodes a 442-amino acid protein that had been reported to interact with DDBl in a proteomic analysis [13]. However, the functional relevance of this interaction was unclear at that time. DDBl is a component of E3 ubiquitin ligase complexes [ 14]. Molecular biological and biochemical studies ultimately showed that thalidomide binds to CRBN and inhibits the associated ubiq-uitin ligase activity. From extensive experimentation with zebrafish and chicks, Handa and coworkers demonstrated that these interactions are responsible for the teratogenic effects of thalidomide. 

In 1996, thalidomide was reapproved for treatment of leprosy, and in 2006, the US Food and Drug Administration granted accelerated approval for use ofthalido-mide in the treatment of newly diagnosed multiple myeloma patients. Identification of the off-targets of thalidomide is expected to contribute greatly to the development of new thalidomide derivatives without teratogenic activity [11,12]. 

Lessons from Isolation of Glyoxalase 1 (GL01) Using Indomethacin 

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