ArticleNature communications2016
Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 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
132 citing papers in PubMed, 234 citations in OpenAlex.
- Bridging E3 Ligase Binding and Targeted Degradation Through Fluorescence Polarization.International journal of molecular sciences · 2026Article
- Computational discovery of HIF-1α/VHL protein-protein interaction inhibitors for hypoxic cell protection.Molecular diversity · 2026Article
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Balancing Stability and Payload Release in Glutathione-Responsive PROTAC Prodrugs Targeting Prostate Cancer.JACS Au · 2026Article
- 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
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors.Nature communications · 2026Article
- Branching beyond bifunctional linkers: synthesis of macrocyclic and trivalent PROTACs.Nature protocols · 2026Review
- Article
- Utilization of Functional Degradation Pathways for the Characterization of Ubiquitin-Proteasome System Tool Compounds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Targeting Protein Tyrosine Phosphatases via PROteolysis-TArgeting Chimeras (PROTACs): Current Developments and Prospects.Molecules (Basel, Switzerland) · 2025Review
- Identification of a Highly Cooperative PROTAC Degrader Targeting GTP-Loaded KRAS(On) Alleles.Journal of the American Chemical Society · 2025Article
- A small-molecule VHL molecular glue degrader for cysteine dioxygenase 1.Nature chemical biology · 2025Article
- Indolequinone-Based Hypoxia-Activated Proteolysis Targeting Chimeras Selectively Degrade BRD4 in Hypoxic Cancer Cells.Journal of the American Chemical Society · 2025Article
- Discovering Uncharted Binding Pockets on E3 Ligases Leads to the Identification of FBW7 Allosteric Modulators.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Conserved lipid metabolic reprogramming confers hypoxic and aging resilience.bioRxiv : the preprint server for biology · 2025Article
- Chromosomal 3p loss and 8q gain drive vasculogenic mimicry via HIF-2α and VE-cadherin activation in uveal melanoma.Cell death and differentiation · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Discovery of a Series of Covalent Ligands That Bind to Cys77 of the Von Hippel-Lindau Tumor Suppressor Protein (VHL).ACS medicinal chemistry letters · 2025Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling.
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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.