ABT-317 (ABT317) is a potent, selective JAK1 inhibitor, inhibits IL-6-stimulated pSTAT3 (TF-1 cells, IC50=16 nM) and IL-2-stimulated pSTAT5 (T-blasts, IC50=30 nM).
ABT 317 shows reduced potency against cytokine signaling pathways mediated by JAK2 (EPO-stimulated pSTAT5 in UT-7 cells, IC50 of 0.50 µM) or TYK2 (IL-12-stimulated pSTAT4 in T-blasts, IC50 of 0.25 µM).
ABT 317 blocks IFN-γ and common γ chain cytokine signaling in vitro.
ABT 317 reduces proinflammatory cytokine signaling in blood T cells and in β cells.
ABT 317 does not affect GM-CSF signaling or blood cell counts.
ABT 317 (10 mg/kg) reduces immune cell infiltration and T-cell proliferation, significantly reduces MHC class 1 expression on the β cell surface and reduces the proportion of CD45+ cells in islets in pre-diabetic NOD mice.
ABT 317 reduces the proportion of effector and memory CD8+ T cells in vivo, reverses newly diagnosed diabetes in NOD mice.