Sigma-Aldrich 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.[1]

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.