ON044580, an α-benzoyl styryl benzyl sulfide, is a potent and non-ATP-competitive JAK2 kinase inhibitor with IC 50 s of 1.23 μM, 1.09 μM for WT and V617F mutant JAK2 , respectively. ON044580 inhibits the JAK2 kinase activity either by binding to the STAT-5 binding domain of JAK2 or by binding to an allosteric site. ON044580 exerts its antiproliferative effect in JAK2 V617F -positive leukemic cells. ON044580 effectively induces apoptosis of Imatinib ( HY-15463 )-resistant chronic myelogenous leukemia (CML) cells. ON044580 also inhibits both WT and T315I mutant forms of the BCR-ABL kinase. ON044580 has the potential for myeloproliferative disorders typified by aberrant JAK/STAT signaling .
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