ArticleInternational journal of molecular sciences2021
Selective Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibition by the SCH772984 Compound Attenuates In Vitro and In Vivo Inflammatory Responses and Prolongs Survival in Murine Sepsis Models.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Prediction models for sepsis-associated acute kidney injury: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Targeting CAFs-derived PCSK6 inhibits redistribution of PD-L1 and restores response of CD8Cell death and differentiation · 2026Article
- The RNA methyltransferase NSUN2 catalyzes 5-methylcytosine (mThe Journal of biological chemistry · 2026Article
- Identification of Novel Extracellular-Signal-Regulated Kinase 2 Inhibitors Through Machine Learning-Driven De Novo Design, Molecular Docking, and Free-Energy Perturbation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Anti- inflammatory effects of Andrographis paniculata (Burm.f.) Wall. Ex Nees leaf in LPS-Induced RAW264.7 macrophages.BMC complementary medicine and therapies · 2025Article
- Developments and Applications of Liver-on-a-Chip Technology-Current Status and Future Prospects.Biomedicines · 2025Review
- GPER1/ACACB are potential target genes associated with intracranial aneurysm and vascular endothelial cell senescence.Neurosurgical review · 2025Article
- Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells.Neurology international · 2024Article
- A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.EMBO molecular medicine · 2024Article
- Mir22hg facilitates ferritinophagy-mediated ferroptosis in sepsis by recruiting the m6A reader YTHDC1 and enhancing Angptl4 mRNA stability.Journal of bioenergetics and biomembranes · 2024Article
- Peroxiredoxin 3 regulates breast cancer progression via ERK-mediated MMP-1 expression.Cancer cell international · 2024Article
- Psilocin suppresses methamphetamine-induced hyperlocomotion and acquisition of conditioned place preference via D2R-mediated ERK signaling.CNS neuroscience & therapeutics · 2023Article
- Article
- Oncology Drug Repurposing for Sepsis Treatment.Biomedicines · 2022Review
- Article
- Strength of Omics in Uncovering Sepsis Mechanisms-A Perspective.Current health sciences journalReview
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Sepsis is the leading cause of death in intensive care units worldwide. Current treatments of sepsis are largely supportive and clinical trials using specific pharmacotherapy for sepsis have failed to improve outcomes. Here, we used the lipopolysaccharide (LPS)-stimulated mouse RAW264.7 cell line and AlphaLisa assay for TNFa as a readout to perform a supervised drug repurposing screen for sepsis treatment with compounds targeting epigenetic enzymes, including kinases. We identified the SCH772984 compound, an extracellular signal-regulated kinase (ERK) 1/2 inhibitor, as an effective blocker of TNFa production in vitro. RNA-Seq of the SCH772984-treated RAW264.7 cells at 1, 4, and 24 h time points of LPS challenge followed by functional annotation of differentially expressed genes highlighted the suppression of cellular pathways related to the immune system. SCH772984 treatment improved survival in the LPS-induced lethal endotoxemia and cecal ligation and puncture (CLP) mouse models of sepsis, and reduced plasma levels of Ccl2/Mcp1. Functional analyses of RNA-seq datasets for kidney, lung, liver, and heart tissues from SCH772984-treated animals collected at 6 h and 12 h post-CLP revealed a significant downregulation of pathways related to the immune response and platelets activation but upregulation of the extracellular matrix organization and retinoic acid signaling pathways. Thus, this study defined transcriptome signatures of SCH772984 action in vitro and in vivo, an agent that has the potential to improve sepsis outcome.
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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.