Biological Activity
AG-490 is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.
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 μM, Stat-3 phosphorylation is decreased by >95% and cell viability is maintained. AG490 at a dose of 10 μM 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 μM. 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 µg) significantly attenuates ʎ-carrageenan-induced thermal hyperalgesia in a dose-dependent manner. AG490 also reduces mechanical hyperalgesia[4].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.