ArticleJournal of medicinal chemistry2025
Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38α Mitogen-Activated Protein Kinase Inhibitors.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
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Who cites it
2 citing papers in PubMed.
- Cancer therapy-related cognitive impairment, part 1: an integrative clinical-mechanistic framework from phenotypes to convergent neurobiological pathways.Pharmacological reports : PR · 2026Review
- Dual Inhibitors of p38α Mitogen-Activated Protein Kinase and Butyrylcholinesterase for the Modulation of Neuroinflammation and Cognitive Dysfunction.Journal of medicinal chemistry · 2026Article
Corrections and comments
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Authors and funding
28 authors.
Funding
Abstract
The currently approved drugs for the treatment of Alzheimer's disease (AD) fail to address its interconnected pathological processes. Inhibition of butyrylcholinesterase (BChE) and p38α mitogen-activated protein kinase (p38α MAPK) offers an innovative dual approach to mitigate two major drivers of neurodegeneration in AD: cholinergic deficit and neuroinflammation. Using structure-based drug design and a library of known p38α MAPK inhibitors, we developed first-in-class, selective dual BChE/p38α MAPK inhibitors with balanced activity against both targets. The X-ray crystal structures of the two most promising molecules bound to both enzymes were solved. Those ligands effectively reduced the production of proinflammatory markers in vitro and ex vivo in phytohemagglutinin/lipopolysaccharide neuroinflammation models. Remarkably, these compounds also significantly improved cognition in scopolamine- and lipopolysaccharide-induced models of cognitive dysfunction in mice. Because our dual-acting inhibitors target both the symptoms and the underlying neuropathology, they offer an innovative and comprehensive strategy to combat AD.
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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.