ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2014
Target engagement analysis and link to pharmacodynamic endpoint for a novel class of CNS-penetrant and efficacious p38α MAPK inhibitors.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Phytotherapy in precision medicine era: deciphering herbal modulation of multi-omic biomarkers for cardiovascular metabolic syndrome remodeling.Frontiers in medicine · 2026Article
- A Selective and Brain Penetrant p38αMAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction.Journal of medicinal chemistry · 2019Review
- p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology.Alzheimer's research & therapy · 2016Article
- FOXO3-NF-κB RelA Protein Complexes Reduce Proinflammatory Cell Signaling and Function.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- APOE-modulated Aβ-induced neuroinflammation in Alzheimer's disease: current landscape, novel data, and future perspective.Journal of neurochemistry · 2015Review
- Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models.ACS chemical neuroscience · 2015Article
- Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats.Journal of Alzheimer's disease : JAD · 2015Article
- Amyloid-β pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo.The Journal of biological chemistry · 2014Article
- The p38alpha mitogen-activated protein kinase limits the CNS proinflammatory cytokine response to systemic lipopolysaccharide, potentially through an IL-10 dependent mechanism.Journal of neuroinflammation · 2014Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The protein kinase, p38α MAPK, is a key intracellular transducer of stressor-induced neuroinflammatory responses and, as such, is of high interest as a potential therapeutic target. We recently reported the synthesis and evaluation of first-in-class CNS-penetrant and highly specific p38 MAPK inhibitors that avoid target crossover issues seen in popular small molecule p38 MAPK inhibitors used in hundreds of previous reports. The novel p38 MAPK inhibitors, represented in this study by MW181, are efficacious in vivo. Pharmacodynamic actions include attenuation of stressor-induced increases in brain proinflammatory cytokine levels. We report here more detailed analyses of MW181 target engagement and specific linkage to the downstream increase in glia proinflammatory cytokine production. In vivo validation included demonstration that oral administration of MW181 suppresses lipopolysaccharide-induced increases in mouse brain IL-1β, TNFα, IL-6, IL-10, and CXCL1 but not in a drug-resistant p38α MAPK mutant mouse.
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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.