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Reporter-based Growth Assay for Systematic Analysis of Protein Degradation
Published on: November 6, 2014
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GSPT1 degraders: research progress, development strategies and challenges.
Chen Liu1, Hongkang Peng1, Peng Chen1
1School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Bioorganic & Medicinal Chemistry
|September 26, 2025
Summary
Targeting GSPT1, previously undruggable, is now possible using Cereblon E3 Ligase Modulators (CELMoDs) to degrade the protein. This breakthrough offers a new therapeutic strategy for GSPT1-related cancers.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- GSPT1 dysregulation is implicated in cancer development and progression.
- GSPT1's lack of binding pockets made it an undruggable target.
- Cereblon E3 Ligase Modulators (CELMoDs) offer a novel approach to target GSPT1.
Purpose of the Study:
- To review the progress of GSPT1 degraders.
- To emphasize the design, activity studies, and development strategies of GSPT1 degraders.
- To provide insights for future GSPT1 degrader development.
Main Methods:
- Review of recent studies on CELMoDs and GSPT1 degradation.
- Analysis of GSPT1 degrader design principles.
- Evaluation of activity studies and clinical trial progress.
Main Results:
- CELMoDs induce GSPT1 degradation by recruiting it to Cereblon.
- Several selective GSPT1 degraders have advanced to clinical trials.
- This approach presents a viable therapeutic strategy for GSPT1-related cancers.
Conclusions:
- GSPT1 degraders represent a promising therapeutic avenue for cancer treatment.
- Further development of GSPT1 degraders is warranted.
- CELMoDs have overcome the 'undruggable' nature of GSPT1.
