ArticleNature chemical biology2020
Rational discovery of molecular glue degraders via scalable chemical profiling.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 173 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
173 citing papers in PubMed.
- Dual E3 ligase recruitment by monovalent degraders for tunable SMARCA 2/4 degradation.Nature chemical biology · 2026Article
- Leveraging high-throughput proteomics and AI-based protein folding to accelerate VAV1 molecular glue discovery.Nature communications · 2026Article
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Article
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Assessing the Stability of Molecular Glues with Weighted Ensemble Simulations.Journal of chemical theory and computation · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Drug Discovery of Allosteric Molecular Glue Degraders (aMGDs): Expanding the Landscape of Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2.Nature biotechnology · 2026Article
- A phenotypic screen enables high-throughput target-first discovery of molecular glue degraders.Nature biotechnology · 2026Article
- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
- Structural diversity and chemical space analysis of a PROTAC database using unsupervised machine learning.Scientific reports · 2026Article
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Deep learning-driven decoding of ubiquitination: from regulatory mechanisms to targeted protein degradation.Biology direct · 2026Review
- Turning KEAP1 against NRF2.Nature chemical biology · 2026Article
113 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
Targeted protein degradation is a new therapeutic modality based on drugs that destabilize proteins by inducing their proximity to E3 ubiquitin ligases. Of particular interest are molecular glues that can degrade otherwise unligandable proteins by orchestrating direct interactions between target and ligase. However, their discovery has so far been serendipitous, thus hampering broad translational efforts. Here, we describe a scalable strategy toward glue degrader discovery that is based on chemical screening in hyponeddylated cells coupled to a multi-omics target deconvolution campaign. This approach led us to identify compounds that induce ubiquitination and degradation of cyclin K by prompting an interaction of CDK12-cyclin K with a CRL4B ligase complex. Notably, this interaction is independent of a dedicated substrate receptor, thus functionally segregating this mechanism from all described degraders. Collectively, our data outline a versatile and broadly applicable strategy to identify degraders with nonobvious mechanisms and thus empower future drug discovery efforts.
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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.