ArticleChemistry & biology2008
Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells.
Article in Chemistry & biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,110 papers, 2 of them syntheses that pooled it.
What it found
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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
1,110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,846 citations in OpenAlex.
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- From Tradition to Innovation: Acupuncture Therapies Targeting Ferroptosis in Neurological Disorders.Brain and behavior · 2025Pooled it
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Pterostilbene Attenuates Neuronal Ferroptosis After Traumatic Brain Injury: Involvement of the SIRT1/PGC-1α/NRF2 Signaling Pathway.Molecular neurobiology · 2026Article
- The impact of fusaric acid on oxidative stress, ferritinophagy, and ferroptosis pathways: a review.Archives of toxicology · 2026Review
- Article
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- Engineered Substrates for a Sulfurtransferase Enhance Endogenous Hydropersulfides and Inhibit Ferroptosis.Angewandte Chemie (International ed. in English) · 2026Article
- Nerve injury-induced protein 2 preserves lysosomal membrane integrity to suppress ferroptosis.eLife · 2026Article
- Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.Neural regeneration research · 2026Article
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- An iron logic unites bacterial and cancer persister cells.Nature reviews. Molecular cell biology · 2026Article
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).Molecular medicine reports · 2026Review
- Isothiocyanates as Ferroptosis Inducers to Promote Cancer Cell Death.Phytotherapy research : PTR · 2026Review
- PLA2G2F suppresses ferroptosis through phospholipid remodeling.Nature structural & molecular biology · 2026Article
- The role of ferroptosis in the pathogenesis and treatment of breast cancer.Journal of translational medicine · 2026Review
- Inhibition of DLX6 sensitizes lung adenocarcinoma to cisplatin via GPX4-dependent ferroptosis.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Concurrent Stereotactic Body Radiation Therapy and KRAS Inhibition Synergistically Improve Pre-clinical Pancreatic Cancer Treatment.bioRxiv : the preprint server for biology · 2026Article
1,050 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
Abstract
We screened small molecules to identify two compounds, which we named RSL3 and RSL5, that have increased lethality in the presence of oncogenic RAS. Counter screening with biologically active compounds defined aspects of the mechanism of action for RSL3 and RSL5, such as a nonapoptotic, MEK-dependent, and iron-dependent oxidative cell death. Erastin, a previously reported compound with RAS-selective lethality, showed similar properties. RNA interference experiments targeting voltage-dependent anion channel 3 (VDAC3), a target of erastin, demonstrated that RSL5 is a scaffold that acts through VDACs to activate the observed pathway. RSL3 activated a similar death mechanism but in a VDAC-independent manner. We found that cells transformed with oncogenic RAS have increased iron content relative to their normal cell counterparts through upregulation of transferrin receptor 1 and downregulation of ferritin heavy chain 1 and ferritin light chain.
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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.