ArticleNature chemistry2019
Diverse compounds from pleuromutilin lead to a thioredoxin inhibitor and inducer of ferroptosis.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 223 citations in OpenAlex.
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- MESH1-mediated coenzyme A degradation drives ferroptosis sensitivity and muscle pathology.The Journal of clinical investigation · 2026Article
- Advances in ferroptosis for castration-resistant prostate cancer treatment: novel drug targets and combination therapy strategies.Prostate cancer and prostatic diseases · 2026Review
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.The Journal of clinical investigation · 2025Article
- Targeting ALDH16A1 mediated thioredoxin lysosomal degradation to enhance ferroptosis susceptibility in SMARCA4-deficient NSCLC.Nature communications · 2025Article
- Article
- Combination of machine learning and protein‑protein interaction network established one ATM‑DPP4‑TXN ferroptotic diagnostic model with experimental validation.Molecular medicine reports · 2025Article
- Prospects for ferroptosis therapies in cancer.Nature cancer · 2025Review
- MicroRNAs at the crossroads of exercise and ferroptosis: a regulatory bridge.Clinical and experimental medicine · 2025Review
- Protein covariation networks for elucidating ferroptosis inducer mechanisms and potential synergistic drug targets.Communications biology · 2025Article
- Identification of a Selective Anticancer Agent from a Collection of Complex-And-Diverse Compounds Synthesized from Stevioside.Journal of the American Chemical Society · 2025Article
- Current Status and Future Directions of Ferroptosis Research in Breast Cancer: Bibliometric Analysis.Interactive journal of medical research · 2025Article
- Unifying principles for the design and evaluation of natural product-inspired compound collections.Chemical science · 2025Review
- Ferroptosis and bone health: bridging the gap between mechanisms and therapy.Frontiers in immunology · 2025Review
- Synthesis and biological activity evaluation of a novel pleuromutilin derivative 22-((2-methyl-1-(1H-pyrrole-2-carboxamido)propan-2-yl)thio)-deoxypleuromutilin.Frontiers in pharmacology · 2025Article
- Article
- Chloroformate-mediated ring cleavage of indole alkaloids leads to re-engineered antiplasmodial agents.Organic & biomolecular chemistry · 2024Article
- Article
- Fundamentals of redox regulation in biology.Nature reviews. Molecular cell biology · 2024Review
49 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
The chemical diversification of natural products provides a robust and general method for the creation of stereochemically rich and structurally diverse small molecules. The resulting compounds have physicochemical traits different from those in most screening collections, and as such are an excellent source for biological discovery. Herein, we subject the diterpene natural product pleuromutilin to reaction sequences focused on creating ring system diversity in few synthetic steps. This effort resulted in a collection of compounds with previously unreported ring systems, providing a novel set of structurally diverse and highly complex compounds suitable for screening in a variety of different settings. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide is an inhibitor of thioredoxin, a key component of the antioxidant system in the cell. Ferroptocide positively modulates the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.
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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.