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Updated: Apr 18, 2026
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
14.0K
[Thalidomide teratogenicity and its direct target identification].
Nihon Rinsho. Japanese Journal of Clinical Medicine
|January 29, 2015
Summary
Thalidomide causes severe birth defects, but is now used for multiple myeloma. Researchers identified cereblon as the drug's primary target responsible for its teratogenic effects.
Area of Science:
- Pharmacology
- Teratology
- Molecular Biology
Background:
- Thalidomide, initially a sedative, caused severe birth defects (e.g., amelia, phocomelia) globally.
- Despite its teratogenicity, thalidomide is now a controlled therapeutic for multiple myeloma.
Purpose of the Study:
- To review thalidomide teratogenicity.
- To recount the identification of cereblon as thalidomide's direct target.
- To discuss recent advancements in cereblon research.
Main Methods:
- Utilized novel affinity bead technology.
- Biochemical assays to identify direct protein targets.
Main Results:
- Identified cereblon as the primary direct target protein responsible for thalidomide's teratogenic effects in 2010.
- Established a link between cereblon and thalidomide-induced developmental abnormalities.
Conclusions:
- Cereblon is the key mediator of thalidomide's teratogenicity.
- Understanding the thalidomide-cereblon interaction is crucial for safe therapeutic use and drug development.
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