ArticleNature communications2024
Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The trial behind it
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Who cites it
14 citing papers in PubMed.
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Discovery of PROTACs recruiting the E3 ligase CHIP.RSC chemical biology · 2026Article
- Pocket-PROTACs: an interpretable pocket-aware deep learning framework for predicting PROTAC-induced protein degradation.Bioinformatics (Oxford, England) · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- Structure of the E3 ligase CRL2Cell reports · 2026Article
- Article
- Minute amounts of helicase-deficient truncated RECQL4 are sufficient for DNA replication.EMBO reports · 2026Article
- KLHDC3 deficiency in mice reveals essential roles in development, survival, and adiposity via the DesCEND ubiquitin pathway.BMC genomics · 2026Article
- Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation.Drug development research · 2025Review
- Review
- Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation.Nature structural & molecular biology · 2025Article
- Article
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases.FEBS letters · 2025Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2. Ligands were identified that engage the C-degron binding site in KLHDC2, subjected to structure-based improvement, and linked to JQ1 for BET-family neo-substrate recruitment. Consideration of the exit vector emanating from the ligand engaged in KLHDC2's U-shaped degron-binding pocket enabled generation of SJ46421, which drives formation of a remarkably cooperative, paralog-selective ternary complex with BRD3
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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.