ArticleNature chemical biology2013
Allosteric inhibition of hypoxia inducible factor-2 with small molecules.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
180 citing papers in PubMed, 297 citations in OpenAlex.
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance.Cancer pathogenesis and therapy · 2026Review
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Divergent Roles of HIF-1α and HIF-2α in Embryonic Development and Early Pregnancy.International journal of molecular sciences · 2026Review
- Review
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
- Renal surgery following HIF-2α antagonist therapy: Surgical indications, outcomes and growth kinetics.Urologic oncology · 2025Article
- Use of High Pressure NMR Spectroscopy to Rapidly Identify Proteins with Internal Ligand-Binding Voids.bioRxiv : the preprint server for biology · 2025Article
- Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- Requirement for Cyclin D1 Underlies Cell-Autonomous HIF2 Dependence in Kidney Cancer.Cancer discovery · 2025Article
- Review
- Interactions Between Non-Coding RNAs and HIF-1alpha in the Context of Colorectal Cancer.Biomolecules · 2025Review
120 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in many cancers where they frequently promote the expression of protumorigenic pathways. Though transcription factors are typically considered 'undruggable', the PAS-B domain of the HIF-2α subunit contains a large cavity within its hydrophobic core that offers a unique foothold for small-molecule regulation. Here we identify artificial ligands that bind within this pocket and characterize the resulting structural and functional changes caused by binding. Notably, these ligands antagonize HIF-2 heterodimerization and DNA-binding activity in vitro and in cultured cells, reducing HIF-2 target gene expression. Despite the high sequence identity between HIF-2α and HIF-1α, these ligands are highly selective and do not affect HIF-1 function. These chemical tools establish the molecular basis for selective regulation of HIF-2, providing potential therapeutic opportunities to intervene in HIF-2-driven tumors, such as renal cell carcinomas.
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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.