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Updated: May 16, 2025
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
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Design and synthetic approaches to thalidomide based small molecule degraders
Ajeet Kumar1, Gulshan Kumar2, Nidhi Kalia1
1Department of Chemistry, University of Florida, Gainesville, FL, 32611, United States.
European Journal of Medicinal Chemistry
|May 14, 2025
Summary
Thalidomide derivatives are emerging as promising anticancer drug candidates. These small molecule degraders target key enzymes and E3 ligases, showing significant antitumor responses and improved drug profiles.
Area of Science:
- Drug discovery and development
- Medicinal chemistry
- Oncology
Background:
- Thalidomide, a repurposed drug since 1997 for multiple myeloma, has spurred the development of novel anticancer agents.
- Thalidomide derivatives and analogs leverage its active moiety to inhibit crucial cellular targets like kinases and transcription factors.
Purpose of the Study:
- To review the development of thalidomide-based small molecule degraders.
- To elucidate recent advancements in their synthetic architecture, biomedical applications, and therapeutic potential.
Main Methods:
- Focus on small molecule degraders with tailored synthetic architectures around the thalidomide motif.
- Review of recent developments including pharmacokinetic profiles, protein stability, activity studies, and degradation assays.
Main Results:
- Thalidomide-based degraders demonstrate efficacy in inhibiting enzymes and facilitating selective protein degradation.
- Recent studies show promising pharmacokinetic profiles, enhanced protein stability, and potent antitumor responses.
Conclusions:
- Thalidomide-based small molecule degraders represent a promising class of anticancer drug candidates.
- Ongoing research focuses on optimizing synthetic strategies and evaluating therapeutic efficacy for various cancers.
Keywords:
Antitumor activityDegradation efficiencyIn vitro cytotoxicitySynthetic designThalidomide based degradersMore Related Videos
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