AI Article Synopsis
- Researchers are exploring CSF1R inhibitors as potential treatments for neuroinflammatory diseases like Alzheimer's disease.
- A modified compound was developed that shows strong selectivity and effectiveness in inhibiting CSF1R, which plays a role in neuroinflammation.
- One of the newly synthesized compounds demonstrated significant anti-inflammatory effects in lab models while showing low toxicity, positioning it as a promising candidate for further research.
Article Abstract
We report herein the potential of colony-stimulating factor-1 receptor (CSF1R) inhibitors as therapeutic agents in neuroinflammatory diseases, with a focus on Alzheimer's disease (AD). Employing a carefully modified scaffold, -(4-heterocycloalkyl-2-cycloalkylphenyl)-5-methylisoxazole-3-carboxamide, we identify highly selective and potent CSF1R inhibitors─ and . Molecular docking studies shed light on the binding modes of these key compounds within the CSF1R binding site. Remarkably, kinome-wide selectivity assessment underscores the impressive specificity of for CSF-1R. Notably, emerges as a potent CSF-1R inhibitor with favorable cellular activity and minimal cytotoxicity among the synthesized compounds. Demonstrating efficacy in inhibiting CSF1R phosphorylation in microglial cells and successfully mitigating neuroinflammation in an LPS-induced model, establishes itself as a promising antineuroinflammatory agent.
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| http://dx.doi.org/10.1021/acs.jmedchem.3c02366 | DOI Listing |
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