ReviewChemical Society reviews2022
Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders.
Review in Chemical Society reviews, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 202 citations in OpenAlex.
- Atomic degradation: chemical design strategies and immunotherapeutic mechanisms of radio-PROTACs.Annals of nuclear medicine · 2026Review
- Harnessing the ubiquitin-proteasome system: advances and challenges of PROTACs in breast cancer.Molecular biology reports · 2026Review
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- Performance of Rilpivirine-Based Hydrophobic Tags and PROTACs Directed Against HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- PRMT7 restricts CD8+ T cells expansion via the NF-ΚB pathway.Nature communications · 2026Article
- Computational discovery of HIF-1α/VHL protein-protein interaction inhibitors for hypoxic cell protection.Molecular diversity · 2026Article
- Autonomously Motile Nano-PROTACs Act as Protein-Sweeping Robots to Enhance Targeted Protein Degradation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Computational mapping of productive POI-E3 ligase conformations to guide de novo degrader design: application to WEE1 and PKMYT1 PROTACs.Journal of cheminformatics · 2026Article
- Discovery of SD-2301 as a Highly Potent and Selective PROTAC STAT3 Degrader Capable of Achieving Complete Tumor Regression with Single Administration.Journal of medicinal chemistry · 2026Article
- Mapping Scientific Landscapes and Therapeutic Innovations of Targeted Protein Degradation: A Scientometric Review.Pharmaceutics · 2026Review
- Native Mass Spectrometry Analysis of Cullin-RING Ubiquitin E3 Ligase Complexes in the Context of Targeted Protein Degradation.Analytical chemistry · 2026Article
- Assays for Measuring the Cell Permeability of Proteolysis-Targeting Chimeras (PROTACs): Performance, Correlations, Applicability and Recommendations.Molecular pharmaceutics · 2026Article
- Structure of the E3 ligase CRL2Cell reports · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Metastable Protein-Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1-VHL System.JACS Au · 2026Article
- Intracellular sclerostin promotes tumor progression and metastasis as a potential therapeutic target in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- Discovery of a Highly Potent and Selective ENL Degrader.Journal of medicinal chemistry · 2026Article
- Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors.Nature communications · 2026Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The von Hippel-Lindau (VHL) Cullin RING E3 ligase is an essential enzyme in the ubiquitin-proteasome system that recruits substrates such as the hypoxia inducible factor for ubiquitination and subsequent proteasomal degradation. The ubiquitin-proteasome pathway can be hijacked toward non-native neo-substrate proteins using proteolysis targeting chimeras (PROTACs), bifunctional molecules designed to simultaneously bind to an E3 ligase and a target protein to induce target ubiquitination and degradation. The availability of high-quality small-molecule ligands with good binding affinity for E3 ligases is fundamental for PROTAC development. Lack of good E3 ligase ligands as starting points to develop PROTAC degraders was initially a stumbling block to the development of the field. Herein, the journey towards the design of small-molecule ligands binding to VHL is presented. We cover the structure-based design of VHL ligands, their application as inhibitors in their own right, and their implementation into rationally designed, potent PROTAC degraders of various target proteins. We highlight the key findings and learnings that have provided strong foundations for the remarkable development of targeted protein degradation, and that offer a blueprint for designing new ligands for E3 ligases beyond VHL.
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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.