A new screen platform named DEFUSE (DEath FUSion Escape) enables high-throughput discovery of small molecule protein degraders. DEFUSE identified SKPer1, a molecule that works by inducing proximity between an oncogenic driver and an E3 ligase, opening new avenues for targeted protein degradation.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 /Â 30Â days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Dale, B. et al. Advancing targeted protein degradation for cancer therapy. Nat. Rev. Cancer 21, 638–654 (2021). This review discusses molecular glue degraders as potential solutions for ‘undruggable’ disease drivers.
Schapira, M., Calabrese, M. F., Bullock, A. N. & Crews, C. M. Targeted protein degradation: expanding the toolbox. Nat. Rev. Drug Discov. 18, 949–963 (2019). This review discusses the advantage of targeted protein degraders over traditional occupancy-based inhibitors.
Hinterndorfer, M. et al. Targeted protein degradation for cancer therapy. Nat. Rev. Cancer https://doi.org/10.1038/s41568-025-00817-8 (2025). This review summarizes various TPD modalities and their prospects as new cancer therapeutics.
Mayor-Ruiz, C. et al. Rational discovery of molecular glue degraders via scalable chemical profiling. Nat. Chem. Biol. 16, 1199–1207 (2020). This study presents the discovery and characterization of a molecular glue degrader of cyclin K.
Garber, K. The glue degraders. Nat. Biotechnol. 42, 546–550 (2024). This news feature profiles approaches to discovering molecular glue degraders.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Chu, Y. et al. A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02793-8 (2025).
Rights and permissions
About this article
Cite this article
A phenotypic screen enables high-throughput target-first discovery of molecular glue degraders. Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02794-7
Published:
DOI: https://doi.org/10.1038/s41587-025-02794-7
