AG-490

AG-490 is a potent inhibitor of the JAK-2 tyrosine kinase. In acute lymphoblastic leukemia (ALL) cells, which abundantly express JAK-2, AG-490 dose-dependently inhibited DNA synthesis, blocked cell growth and induced apoptosis. At 5 µM, AG-490 almost completely blocked the growth of all pre-B ALL cells but had no significant effect on the growth of mitogen-stimulated normal B or T cells, B-cell lymphoma or T-cell leukemia cells. AG-490 does not significantly inhibit other kinases such as Lck, Lyn, Btk, Syk and Src. It blocks interleukin-7-induced JAK kinase activity in T-cells (JAK-1, JAK-3) and the consequent phosphorylation of PI-3 kinase. AG-490 is cell permeable and is a valuable tool for studying the cellular role of JAK kinases in signal transduction.