ArticleACS central science2023
Rational Chemical Design of Molecular Glue Degraders.
Article in ACS central science, 2023. 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 81 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
81 citing papers in PubMed, 166 citations in OpenAlex.
- Molecular glues: Recent advances in cereblon substrate identification and mechanistic insights.Smart molecules : open access · 2026Article
- Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery.Medicinal research reviews · 2026Review
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ubiquitin family as novel protein partners for molecular glues.npj drug discovery · 2026Review
- Spop-binding bifunctional degraders: a novel approach for cancer immunotherapy.Journal of advanced research · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Tipping the balance: synthesis and evaluation of centrinone-based degraders of polo-like kinase 4.RSC chemical biology · 2026Article
- Molecular glue degraders: Rational design, specificity engineering, and advanced delivery.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Mild Transsulfinamidation Enables Rapid Access to Sulfinamides, Sulfonamides, and Sulfonimidamides.Organic letters · 2026Article
- Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.Nature chemical biology · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Article
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.Journal of chemical information and modeling · 2026Article
- An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders.bioRxiv : the preprint server for biology · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Targeted protein degradation with molecular glue degraders has arisen as a powerful therapeutic modality for eliminating classically undruggable disease-causing proteins through proteasome-mediated degradation. However, we currently lack rational chemical design principles for converting protein-targeting ligands into molecular glue degraders. To overcome this challenge, we sought to identify a transposable chemical handle that would convert protein-targeting ligands into molecular degraders of their corresponding targets. Using the CDK4/6 inhibitor ribociclib as a prototype, we identified a covalent handle that, when appended to the exit vector of ribociclib, induced the proteasome-mediated degradation of CDK4 in cancer cells. Further modification of our initial covalent scaffold led to an improved CDK4 degrader with the development of a but-2-ene-1,4-dione ("fumarate") handle that showed improved interactions with RNF126. Subsequent chemoproteomic profiling revealed interactions of the CDK4 degrader and the optimized fumarate handle with RNF126 as well as additional RING-family E3 ligases. We then transplanted this covalent handle onto a diverse set of protein-targeting ligands to induce the degradation of BRD4, BCR-ABL and c-ABL, PDE5, AR and AR-V7, BTK, LRRK2, HDAC1/3, and SMARCA2/4. Our study undercovers a design strategy for converting protein-targeting ligands into covalent molecular glue degraders.
Identifiers
What OpenQuestion holds
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.