ArticleScience (New York, N.Y.)2024
Continuous evolution of compact protein degradation tags regulated by selective molecular glues.
Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 71 citations in OpenAlex.
- Selective and Potent First-in-Class CRBN-Dependent Molecular Glue Degraders of WW Domain-Binding Protein 4.Angewandte Chemie (International ed. in English) · 2026Article
- Protein turnover in plants-cost of synthesis, repair, and crop engineering opportunities.Plant physiology · 2026Review
- Article
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Targeted KRASG12V Degradation In Vivo Elicits Lung Adenocarcinoma Regression with Subsequent Relapse from Dysregulated Proteolysis.Cancer research · 2026Article
- A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2.Nature biotechnology · 2026Article
- rRGD3International journal of molecular sciences · 2026Article
- The benchmarking and application of tag-degraders in vivo to validate therapeutic targets.Nature communications · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Phage-assisted evolution of allosteric protein switches.Nature communications · 2026Article
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.Journal of chemical information and modeling · 2026Article
- Development of PolyHis-Targeting PROTAC Degraders.Angewandte Chemie (International ed. in English) · 2026Article
- A Degron Decoy System Co-opts Pathological Seeding to Enable Clearance of Multimeric α-Synuclein.bioRxiv : the preprint server for biology · 2026Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.Nature communications · 2025Article
- Orthogonal IMiD-Degron Pairs Induce Selective Protein Degradation in Cells.ACS chemical biology · 2025Article
- A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation.Nature communications · 2025Article
- Targeted degradation of endogenous YAP by nanobody bioPROTAC inhibits tumor progression.Nature communications · 2025Article
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Conditional protein degradation tags (degrons) are usually >100 amino acids long or are triggered by small molecules with substantial off-target effects, thwarting their use as specific modulators of endogenous protein levels. We developed a phage-assisted continuous evolution platform for molecular glue complexes (MG-PACE) and evolved a 36-amino acid zinc finger (ZF) degron (SD40) that binds the ubiquitin ligase substrate receptor cereblon in complex with PT-179, an orthogonal thalidomide derivative. Endogenous proteins tagged in-frame with SD40 using prime editing are degraded by otherwise inert PT-179. Cryo-electron microscopy structures of SD40 in complex with ligand-bound cereblon revealed mechanistic insights into the molecular basis of SD40's activity and specificity. Our efforts establish a system for continuous evolution of molecular glue complexes and provide ZF tags that overcome shortcomings associated with existing degrons.
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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.