Selectively\nAntagonizing the NOD1-Mediated Inflammatory\nSignaling Pathway Mitigates the Gastric Inflammation Induced by Helicobacter pylori Infection

Helicobacter pylori (H. pylori) infection is characterized by the complex\ninterplay between H. pylori and gastric\ndisorders. It has been established that NOD1 can be activated by the\npeptidoglycan (PGN) present in the cell wall of H.\npylori, serving as a key mediator of inflammation\nand initiating the RIP2/NF-κB and MAPK inflammatory signaling\npathways. In this article, we reported on the development of a 2-chloroquinazolin-4-ol\nderivative <b>66</b> as a potent and selective antagonist of\nboth human and mouse NOD1, which effectively inhibited the expression\nof inflammatory cytokines (IL-6, TNF-α) and chemokines (CXCL1,\nCXCL8) in immune and epithelial cells, as well as inflammatory cytokines\n(KC, IL-6) in a H. pylori-induced murine\nmodel of gastritis following oral administration. This study laid\na foundation for treating gastritis induced by H. pylori infection.