ArticleCell death & disease2012
Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 269 papers.
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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
269 citing papers in PubMed, 439 citations in OpenAlex.
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- HIGH DOSE GAMMAHERPESVIRUS INFECTION IN MACROPHAGES RESULTS IN INFLAMMATORY MULTIMODAL CELL DEATH.bioRxiv : the preprint server for biology · 2026Article
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- Neuroinflammation and Graft Survival in Pluripotent Stem Cell-Derived Therapies for the Central Nervous System.Journal of neurochemistry · 2026Review
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- Kidney‑enriched lipid nanoparticles delivering ANXA2 alleviate renal ischemia-reperfusion injury via CHMP2A-mediated necroptosis inhibition.Journal of nanobiotechnology · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Inhibition of RIPK1/RIPK3-MLKL inflammatory signaling pathway activation attenuates preterm birth.Cell death discovery · 2026Article
- RIP kinase inhibition with Necrostatin-1 improves human marginal mass islet graft survival and function for the management of type 1 diabetes.Cell death & disease · 2026Article
- Molecular and Cellular Mechanisms of Myocardial Ischemia and Reperfusion Injury: A Narrative Review.Cells · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Receptor-Interacting Protein Kinase 1 (RIPK1): A Potential Therapeutic Target in Ischemic Stroke.Molecular neurobiology · 2026Review
- Gasdermin D Cleavage and Cytokine Release, Indicative of Pyroptotic Cell Death, Induced by Ophiobolin A in Breast Cancer Cell Lines.International journal of molecular sciences · 2026Article
- PANoptosis in Cytokine Release Syndrome: Bridging the Gap between Inflammation and Cell Death.Current pharmaceutical design · 2026Review
- Delayed necrostatin-1s infusion attenuates cystic white matter injury in preterm fetal sheep.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Caspases and programmed cell death in sepsis: mechanisms, pathophysiology, and therapeutic targets.Frontiers in immunology · 2026Review
- RIPK1 inhibition reduces biliary injury and fibrosis in primary sclerosing cholangitis.Science advances · 2025Article
- RIPK1 Drives JAK1-STAT3 Signaling to Promote CXCL1-Mediated Neutrophil Recruitment in Sepsis-Induced Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- iPLA2β Protects Retinal Pigment Epithelium From Ferroptosis in a Sodium Iodate-Induced Model of Dry AMD.Investigative ophthalmology & visual science · 2025Article
209 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × less effective than Nec-1 in inhibiting human RIPK1 kinase activity in vitro, it was only 10 times less potent than Nec-1 and Nec-1s in a mouse necroptosis assay and became even equipotent at high concentrations. Along the same line, in vivo, high doses of Nec-1, Nec-1i and Nec-1s prevented tumor necrosis factor (TNF)-induced mortality equally well, excluding the use of Nec-1i as an inactive control. Paradoxically, low doses of Nec-1 or Nec-1i, but not Nec -1s, even sensitized mice to TNF-induced mortality. Importantly, Nec-1s did not exhibit this low dose toxicity, stressing again the preferred use of Nec-1s in vivo. Our findings have important implications for the interpretation of Nec-1-based data in experimental disease models.
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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.