AG-490

133550-30-8

C17H14N2O3

DMSO : >= 50 mg/mL (169.89 mM)

JAK/STAT Signaling; Protein Tyrosine Kinase/RTK; Autophagy; JAK/STAT Signaling; Stem Cell/Wnt

AG-490 is an tyrosine kinase inhibitor, inhibits EGFR and Stat-3. IC50 & Target: EGFR and Stat-3^[1] In Vitro: AG490 inhibits the activation of Stat-3 by selectively blocking JAK2. AG490 is used to selectively inhibit JAK/Stat-3 activation. At a dose of 10 uM, Stat-3 phosphorylation is decreased by >95% and cell viability is maintained. AG490 at a dose of 10 uM results in >95% decrease in pStat-3 in EGF-stimulated A431 cells with no effect on Stat-3 mass^[1]. AG-490 is a potent inhibitor of the JAK3/STAT, JAK3/AP-1, and JAK3/MAPK pathways and their cellular consequences. AG-490 abolishes IL-2-inducible [³H]thymidine incorporation in a dose-dependent manner, displaying an IC₅₀ of 25 uM. AG-490 potently inhibits IL-2-mediated proliferation in T cells, results distinct from previous studies that showed this agent induced apoptosis in ALL cells while exerting apparently no effects on the growth of mitogen-stimulated normal T cells^[2]. In Vivo: AG490 significantly inhibits the development of type 1 diabetes (T1D) (p?=?0.02, p?=?0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 (1 mg/mouse) markedly results in disease remission in treated animals (n=23) in comparision to the absolute inability (0%; 0/10, p=0.003, Log-rank test) of DMSO and sustained eugluycemia is maintained for several months following drug withdrawal^[3]. AG490 (1-10 ug) significantly attenuates ?-carrageenan-induced thermal hyperalgesia in a dose-dependent manner. AG490 also reduces mechanical hyperalgesia^[4].