GPR34 Antagonist, T8848

GPR34 Antagonist, T8848 may be used to investigate the effects of pharmacological inhibition of GPR34 on microglial dysfunction and neuroinflammation in Alzheimer’s disease (AD) mouse models.

GPR34 antagonist that potently inhibits neuroinflammation by blocking PI3K-AKT and ERK pathways, selectively reducing cytokine release.The GPR34 antagonist T8848 selectively targets G-protein coupled receptor 34 (GPR34), inhibiting LysoPS and myelin debris-induced IL-1β and IL-6 expression in microglia with high specificity. In vitro, T-8848 is applied at of 100 μg/mL, effectively reducing pro-inflammatory cytokine release. In vivo, at 10 mg/kg (i.p.) administered over 18-days in C57BL/6J mice and Gpr34-specific knockout mice (e.g., Gpr34fl/flCx3cr1CreER), it lessens neuroinflammation, demyelination, and tissue damage in models of multiple sclerosis and stroke. Mechanistically, T 8848 blocks GPR34-mediated phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) and extracellular signal-regulated kinase (ERK) pathways, suppressing downstream inflammatory gene expression and cytokine release.