AR-A014418

AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor (IC₅₀=104 nM; K_i=38 nM)^[1]. IC50 & Target: IC50: 104 nM (GSK3β); Ki: 38 nM (GSK3β)^[1] In Vitro: AR-A014418 blocks the phosphorylation of tau at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein, with an IC₅₀ of 2.7 μM, and protects cultured N2A cells from death cuased by PI3K/PKB pathway blockage. AR-A014418 also shows inhibitory effect on neurodegeneration mediated by beta-amyloid peptide in hippocampal slices^[1]. AR-A014418 decreases neuroendocrine markers and suppresses neuroblastoma cell growth in NGP and SH-5Y-SY cells^[2]. In Vivo: AR-A014418 (0-4 mg/kg, i.p.) delays the onset of symptoms, enhances motor activity, blocks disease progression, and postpons the endpoint of the disease in ALS mouse model with the G93A mutant human SOD1^[3]. Furthermore, AR-A014418 suppresses acetic acid- and formalin-induced nociception in mice via modulating NMDA and metabotropic receptor signaling as well as TNF-α and IL-1β transmission in the spinal cord^[4].