ArticleNature communications2017
Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 236 citations in OpenAlex.
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- A pharmacological modality to sequester homomeric proteins.Nature chemical biology · 2026Article
- A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly.ACS central science · 2026Article
- Structural diversity and chemical space analysis of a PROTAC database using unsupervised machine learning.Scientific reports · 2026Article
- Targeting drug resistance in breast cancer: a dual-perspective landscape analysis of PROTACs from bench to bedside.Breast cancer research : BCR · 2026Review
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Branching beyond bifunctional linkers: synthesis of macrocyclic and trivalent PROTACs.Nature protocols · 2026Review
- A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026Article
- Design and synthesis of novel HDAC6 inhibitor dimer as HDAC6 degrader for cancer treatment by palladium catalysed dimerisation.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation.Nature communications · 2025Article
- Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge.Journal of molecular biology · 2025Review
- Review
- Deubiquitinase-Targeting Chimeras Mediated Stabilization of Tumor Suppressive E3 Ligase Proteins as a Strategy for Cancer Therapy.Journal of the American Chemical Society · 2025Article
- Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.Acta pharmaceutica Sinica. B · 2025Article
- Advancing Design Strategy of PROTACs for Cancer Therapy.MedComm · 2025Review
- Methods to accelerate PROTAC drug discovery.The Biochemical journal · 2025Review
- PHD3-VHL axis controls HIV-2 infection through oxygen-dependent hydroxylation and degradation of Vpx.PLoS pathogens · 2025Article
- Rational Design of PROTAC Linkers Featuring Ferrocene as a Molecular Hinge to Enable Dynamic Conformational Changes.Journal of the American Chemical Society · 2025Article
- Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer.Nature chemical biology · 2025Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells. We provide proof-of-concept of Homo-PROTACs using diverse molecules composed of two instances of a ligand for the von Hippel-Lindau (VHL) E3 ligase. The most active compound, CM11, dimerizes VHL with high avidity in vitro and induces potent, rapid and proteasome-dependent self-degradation of VHL in different cell lines, in a highly isoform-selective fashion and without triggering a hypoxic response. This approach offers a novel chemical probe for selective VHL knockdown, and demonstrates the potential for a new modality of chemical intervention on E3 ligases.Targeting the ubiquitin proteasome system to modulate protein homeostasis using small molecules has promising therapeutic potential. Here the authors describe Homo-PROTACS: small molecules that can induce the homo-dimerization of E3 ubiquitin ligases and cause their proteasome-dependent degradation.
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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.