ON044580

Description

ON044580, an ?-benzoyl styryl benzyl sulfide, is a potent and non-ATP-competitive JAK2 kinase inhibitor with IC50s of 1.23 ?M, 1.09 ?M 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 JAK2V617F-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.