ArticleCell chemical biology2024
The cyclimids: Degron-inspired cereblon binders for targeted protein degradation.
Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- A Versatile DNA-Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bridging E3 Ligase Binding and Targeted Degradation Through Fluorescence Polarization.International journal of molecular sciences · 2026Article
- A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death.Cell · 2026Article
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.Nature chemical biology · 2026Article
- A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.Nature communications · 2026Article
- Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry.Nature structural & molecular biology · 2026Article
- Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Chemical and Enzymatic Approaches to C-Terminal Cyclic Imide Formation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Tuning the open-close equilibrium of Cereblon with small molecules influences protein degradation.bioRxiv : the preprint server for biology · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- A method for the detection and enrichment of endogenous cereblon substrates.Cell chemical biology · 2025Article
- Design and Application of Cereblon-Recruiting Prodegraders.Journal of the American Chemical Society · 2025Article
- A method for the detection and enrichment of endogenous cereblon substrates.bioRxiv : the preprint server for biology · 2025Article
- A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development.Angewandte Chemie (International ed. in English) · 2025Article
- Cysimiditides: RiPPs with a Zn-Tetracysteine Motif and Aspartimidylation.Biochemistry · 2025Article
- Genesis and regulation of C-terminal cyclic imides from protein damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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9 authors.
Funding
Abstract
Cereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer a facile approach for developing potent and selective bifunctional degraders. Quantitative TR-FRET-based characterization of 60 cyclimid degraders in binary and ternary complexes across different substrates revealed that ternary complex binding affinities correlated strongly with cellular degradation efficiency. Our studies establish the unique properties of the cyclimids as versatile warheads in TPD and a systematic biochemical approach for quantifying ternary complex formation to predict their cellular degradation activity, which together will accelerate the development of ligands that engage CRBN.
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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.