ArticleEuropean journal of pharmacology2020
Modulation of LPS-induced inflammatory cytokine production by a novel glycogen synthase kinase-3 inhibitor.
Article in European journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting autophagy in Duchenne muscular dystrophy: mechanistic insights and emerging therapeutic strategies.Journal of medical genetics · 2026Review
- The Mechanism of Ultrasonic Lysis ofCells · 2026Article
- Neutrophils are key modulators of sex differences in LPS-induced shock in mice.Blood vessels, thrombosis & hemostasis · 2025Article
- Capturing the Effects of Single Atom Substitutions on the Inhibition Efficiency of Glycogen Synthase Kinase-3β Inhibitors via Markov State Modeling and Experiments.Journal of chemical theory and computation · 2024Article
- Mechanistic insights into SARS-CoV-2 spike protein induction of the chemokine CXCL10.Scientific reports · 2024Article
- GSK3β/NF-κB -dependent transcriptional regulation of homeostatic hepatocyteAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Identification of hub genes associated withWorld journal of diabetes · 2024Article
- A kinase to cytokine explorer to identify molecular regulators and potential therapeutic opportunities.eLife · 2024Article
- Quercetin Alleviates Inflammation and Energy Deficiency Induced by Lipopolysaccharide in Chicken Embryos.Animals : an open access journal from MDPI · 2023Article
- Patients with Infections of The Central Nervous System Have Lowered Gut Microbiota Alpha Diversity.Current issues in molecular biology · 2022Article
- Evidence for investigating GSK-3 inhibitors as potential therapeutics for severe COVID-19.Biochemical and biophysical research communications · 2022Article
- Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- MicroRNA-214-3p facilitates M2 macrophage polarization by targeting GSK3B.The Kaohsiung journal of medical sciences · 2022Article
- Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer.Frontiers in immunology · 2022Article
- A novel GSK-3 inhibitor binds to GSK-3β via a reversible, time and Cys-199-dependent mechanism.Bioorganic & medicinal chemistry · 2021Article
- Evidence that knock down of GSK-3β in Chronic Myelogenous Leukemia cells augments IFN-γ-induced apoptosis.Leukemia research · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Sepsis is a serious condition that can lead to long-term organ damage and death. At the molecular level, the hallmark of sepsis is the elevated expression of a multitude of potent cytokines, i.e. a cytokine storm. For sepsis involving gram-negative bacteria, macrophages recognize lipopolysaccharide (LPS) shed from the bacteria, activating Toll-like-receptor 4 (TLR4), and triggering a cytokine storm. Glycogen synthase kinase-3 (GSK-3) is a highly active kinase that has been implicated in LPS-induced cytokine production. Thus, compounds that inhibit GSK-3 could be potential therapeutics for sepsis. Our group has recently described a novel and highly selective inhibitor of GSK-3 termed COB-187. In the present study, using THP-1 macrophages, we evaluated the ability of COB-187 to attenuate LPS-induced cytokine production. We found that COB-187 significantly reduced, at the protein and mRNA levels, cytokines induced by LPS (e.g. IL-6, TNF-α, IL-1β, CXCL10, and IFN-β). Further, the data suggest that the inhibition could be due, at least in part, to COB-187 reducing NF-κB (p65/p50) DNA binding activity as well as reducing IRF-3 phosphorylation at Serine 396. Thus, COB-187 appears to be a potent inhibitor of the cytokine storm induced by LPS.
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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.