ArticleBiotechnology letters2025
Discovery of novel compound IGYZT01060 for inhibition of IRAK-4 enzyme for the treatment of sepsis.
Article in Biotechnology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeThis study aimed at the discovery of a novel chemical entity, IGYZT01060 for inhibiting IRAK-4 (Interleukin-1 receptor-associated kinase 4) and testing its ability to inhibit the IRAK-4 enzyme, that is crucial in the context of sepsis due to its central role in the innate immune response, particularly in mediating inflammatory signals from Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs).
methodsThis study explores the synthesis and characterization of a novel compound, IGYZT01060, designed to inhibit IRAK-4. The inhibitory analysis was carried out in silico, in vitro and in vivo. Molecular docking was done using AutoDock software. The in vitro assays were carried out in LPS induced THP-1 cells. ADME assays were carried out for understanding the drug delivery and distribution pattern. Lastly, in vivo mice sepsis model using intraperitoneally administered LPS and orally administered compound IGYZT01060 was studied estimate the efficacy of compound IGYZT01060.
resultsIn silico docking analyses demonstrated a high affinity of IGYZT01060 for IRAK-4, with target prediction indicating a preference for kinase enzymes. The NMR spectroscopy confirmed the successful synthesis and purity of the compound. In vitro studies revealed that IGYZT01060 effectively inhibits IRAK-4 with an IC
conclusionThe promising IRAK-4 inhibition demonstrated by our compound IGYZT01060, along with its favourable pharmacokinetic profile and significant efficacy in a mice sepsis model, highlights its potential as a powerful therapeutic option for treating inflammatory conditions.
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