ReviewExpert opinion on investigational drugs2009
Can we predict the effects of NF-kappaB inhibition in sepsis? Studies with parthenolide and ethyl pyruvate.
Review in Expert opinion on investigational drugs, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 32 citations in OpenAlex.
- Hyper-inflammation and immunosuppression: redefining sepsis therapy using modern approaches.Frontiers in pharmacology · 2026Review
- Pharmacological Inhibition and Genetic Deletion of Cystathionine Gamma-Lyase in Mice Protects against Organ Injury in Sepsis: A Key Role of Adhesion Molecules on Endothelial Cells.International journal of molecular sciences · 2023Article
- Review
- The Role of Nuclear Factor Kappa B (NF-κB) in Development and Treatment of COVID-19: Review.International journal of molecular sciences · 2022Review
- Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis.Inflammation · 2022Article
- Orexins: A promising target to digestive cancers, inflammation, obesity and metabolism dysfunctions.World journal of gastroenterology · 2021Review
- The Implications of Zinc Therapy in Combating the COVID-19 Global Pandemic.Journal of inflammation research · 2021Review
- Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor.Cancer cell international · 2020Article
- Esmolol inhibits inflammation and apoptosis in the intestinal tissue via the overexpression of NF-κB-p65 in the early stage sepsis rats.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2020Article
- Orexins as Novel Therapeutic Targets in Inflammatory and Neurodegenerative Diseases.Frontiers in endocrinology · 2019Review
- Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality.Critical care medicine · 2013Article
- 2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε.Amino acids · 2012Article
- Anti-inflammatory activity of a novel family of aryl ureas compounds in an endotoxin-induced airway epithelial cell injury model.PloS one · 2012Article
- Ethyl pyruvate preserves IGF-I sensitivity toward mTOR substrates and protein synthesis in C2C12 myotubes.Endocrinology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundBased partially on encouraging findings from preclinical models, interest has grown in therapeutic inhibition of NF-kappaB to limit inflammatory injury during sepsis. However, NF-kappaB also regulates protective responses, and predicting the net survival effects of such inhibition may be difficult.
objectivesTo highlight the caution necessary with this therapeutic approach, we review our investigations in a mouse sepsis model with parthenolide and ethyl pyruvate, two NF-kappaB inhibitors proposed for clinical study.
resultsConsistent with published studies, parthenolide decreased NF-kappaB binding activity and inflammatory cytokine release from lipopolysaccharide (LPS) stimulated RAW 264.7 cells in vitro. In LPS-challenged mice (C57BL/6J), however, while both agents decreased lung and kidney NF-kappaB binding activity and plasma cytokines early (1-3 h), these measures were increased later (6-12 h) in patterns differing significantly over time. Furthermore, despite studying several doses of parthenolide (0.25-4.0 mg/kg) and ethyl pyruvate (0.1-100 mg/kg), each produced small but consistent decreases in survival which overall were significant (p < or = 0.04 for each agent).
conclusionWhile NF-kappaB inhibitors hold promise for inflammatory conditions such as sepsis, caution is necessary. Clear understanding of the net effects of NF-kappaB inhibitors on outcome will be necessary before such agents are used clinically.
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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.