サリドマイド催奇性の原因因子の発見から創薬への展開

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  • Drug development based on identification of a causal factor of thalidomide embryopathy

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Half a century ago, the sedative thalidomide caused one of the worst notorious drug disasters in history, with more than 10,000 babies born with deformities. The drug is now used in the treatment of multiple myeloma. Recently new thalidomide derivatives called immunomodulatory drugs (IMiDs) have been developed. Among them, lenalidomide and pomalidomide have excellent anti-cancer activity. However, the use of them is limited due to its potent teratogenic activity. The mechanism by which IMiDs including thalidomide induce birth defects and therapeutic effects was a long-standing question. Using an affinity beads technology we originally developed, we have identified cereblon(CRBN)as a primary target of IMiDs. CRBN forms an E3 ubiquitin ligase complex. IMiDs alter the activity and induce various biological effects such as teratogenicity, anti-cancer and immunomodulation.Understanding IMiDs and CRBN may lead to uncover new therapeutic pathways for overcoming refractory cancer diseases.

収録刊行物

  • Organ Biology

    Organ Biology 21 (2), 134-140, 2014

    一般社団法人　日本臓器保存生物医学会

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