AI Article Synopsis
- IRAK4 kinase plays a key role in signaling pathways from IL-1 receptors and Toll-like receptors, affecting cytokines and chemokines tied to inflammatory diseases.
- There is a strong push to find specific IRAK4 inhibitors to effectively treat these conditions.
- Researchers used a human whole blood assay to identify new benzolactam IRAK4 inhibitors, successfully discovering a potent compound that significantly inhibits relevant cytokines in living organisms.
Article Abstract
IRAK4 kinase activity transduces signaling from multiple IL-1Rs and TLRs to regulate cytokines and chemokines implicated in inflammatory diseases. As such, there is high interest in identifying selective IRAK4 inhibitors for the treatment of these disorders. We previously reported the discovery of potent and selective dihydrobenzofuran inhibitors of IRAK4. Subsequent studies, however, showed inconsistent inhibition in disease-relevant pharmacodynamic models. Herein, we describe application of a human whole blood assay to the discovery of a series of benzolactam IRAK4 inhibitors. We identified potent molecule that achieves robust in vivo inhibition of cytokines relevant to human disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073891 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.9b00380 | DOI Listing |
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