ArticleCell chemical biology2022
Small-molecule allosteric inhibitors of GPX4.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 85 citations in OpenAlex.
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Degrading GPX4 via Biomimetic Nanoparticle-Mediated In Situ Synthesis of Deep-Learning-Designed Binder-Degron Chimeras for Prostate Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 4-Hydroxytamoxifen induces a noncanonical ferroptosis in lung adenocarcinoma by targeting AKR1B10.Clinical and translational medicine · 2026Article
- Regulation of Glutathione Peroxidase 4 in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging tools to investigate the contribution of selenium to ferroptosis and beyond.Nature chemical biology · 2026Review
- GPX4 in the Tumor Microenvironment: Not Just Inhibiting Ferroptosis, but Immuno-Metabolic Regulation.Biomolecules · 2026Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- What lies beyond thioredoxin reductase? Cyclometallated gold compounds reveal Sec selectivity in glutathione peroxidases.Free radical biology & medicine · 2026Article
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Cardiomyocyte-derived GPX4 stabilizes BNIP3 to facilitate mitophagy and mitigate myocardial ischemia/reperfusion injury.Nature communications · 2026Article
- RS-1: A Novel Hydrophobic Tagging GPX4 Degrader Inducing Ferroptosis and Suppressing Tumor Growth.ACS omega · 2026Article
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- γ-Cyclodextrin/Genistein Inclusion Complex Catalyzes GPx4-Mediated Reduction of Organic/Inorganic Peroxides: Based on SERS and In Silico Research.Foods (Basel, Switzerland) · 2026Article
- Transsulfuration metabolism is essential for ferroptosis resistance in quiescent endothelial cells.Cell death & disease · 2025Article
- Effects of plant-derived dietary antioxidants on Alzheimer's disease: Focus on ferroptosis.Asia Pacific journal of clinical nutrition · 2025Review
- Does ginsenoside Rg1 promote intervertebral disc repair? An experimental study insights into ferroptosis mechanism.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Encouraged by the dependence of drug-resistant, metastatic cancers on GPX4, we examined biophysical mechanisms of GPX4 inhibition, which revealed an unexpected allosteric site. We found that this site was involved in native regeneration of GPX4 under low glutathione conditions. Covalent binding of inhibitors to this allosteric site caused a conformational change, inhibition of activity, and subsequent cellular GPX4 protein degradation. To verify this site in an unbiased manner, we screened a library of compounds and identified and validated that an additional compound can covalently bind in this allosteric site, inhibiting and degrading GPX4. We determined co-crystal structures of six different inhibitors bound in this site. We have thus identified an allosteric mechanism for small molecules targeting aggressive cancers dependent on GPX4.
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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.