LY2784544 is a potent, ATP-competitive inhibitor of janus kinase 2 (JAK2) that less effectively inhibits JAK3 (IC50s = 3 and 48 nM, respectively). It also inhibits JAK2 containing the V617F mutation (IC50 = 20 nM), blocking STAT5 phosphorylation and proliferation of Ba/F3 pro-B-cells expressing this constitutively active JAK2 mutant form. When given by oral gavage, LY2784544 significantly reduces the growth of Ba/F3 pro-B-cells in SCID mice without affecting erythroid progenitors, reticulocytes, or platelets. JAK inhibitors, including LY2784544, may be useful in hematological malignancies.
