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Thalidomide was introduced in 1950s as a safe and effective hypnotic but was subsequently withdrawn from the market due to its devastating teratogenicity in humans. More recently, thalidomide has reemerged as an antineoplastic and immunomodulatory medicine. The teratogenic and immunomodulatory effects of thalidomide have been attributed to direct inhibition of the cereblon-mediated ubiquitin/proteasome pathway. Here we show that cereblon is not involved in the hypnotic effect of thalidomide, using mice that carry a thalidomide-resistant mutant allele of the cereblon gene. Our results suggest the possibility for dissociating the hypnotic effect of thalidomide and its analogs from its teratogenicity.
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This page is a summary of: Hypnotic effect of thalidomide is independent of teratogenic ubiquitin/proteasome pathway, Proceedings of the National Academy of Sciences, August 2020, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.1917701117.
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