ArticleACS chemical biology2025
Orthogonal IMiD-Degron Pairs Induce Selective Protein Degradation in Cells.
Article in ACS chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Article
- Replacing Ecologically Risky Trifluoroacetic Acid and Acetonitrile With Methanesulfonic Acid and Dimethyl Carbonate in High-Performance Liquid Chromatography Analyses of Small Molecule Drugs.Journal of separation science · 2026Article
- A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.Nature communications · 2026Article
- Deciphering the Influence of Side Chains of Short Cationic Hydrophobic Peptides on Macroscopic and Molecular Properties of Mixed Lipid Bilayers.The Journal of membrane biology · 2026Article
- A Degron Decoy System Co-opts Pathological Seeding to Enable Clearance of Multimeric α-Synuclein.bioRxiv : the preprint server for biology · 2026Article
- Controlling CRISPR-Cas9 genome editing in human cells using a molecular glue degrader.Molecular therapy. Nucleic acids · 2025Article
- Designing the Proteome with Chemical Tools: Degrons and Beyond.Chembiochem : a European journal of chemical biology · 2025Review
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24 authors.
Funding
Abstract
Immunomodulatory imide drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide, can be used to induce degradation of a protein of interest that is fused to a short degron motif, which often comprises a zinc finger (ZF). These IMiDs, however, also induce the degradation of endogenous ZF-containing neosubstrates, including IKZF1, IKZF3, and SALL4. To improve degradation selectivity, we took a bump-and-hole approach to design and screen bumped IMiD analogues against 8380 ZF mutants. This yielded a bumped IMiD analogue that induces efficient degradation of a mutant ZF degron, while not affecting other cellular proteins, including IKZF1, IKZF3, and SALL4. In proof-of-concept studies, this system was applied to induce degradation of the optimum degron fused to CDK9, HPRT1, NanoLuc, or TRIM28. We anticipate that this system will be a valuable addition to the current arsenal of degron systems for use in target validation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.