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 dosedependently 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 kinaseactivity 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.
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