ON044580

ON044580 is an effective non-ATP-competitive inhibitor of JAK2, characterized as an ?-benzoylstyrylbenzyl thioether. It exhibits IC50 values of 1.23 ?M for wild type JAK2 and 1.09 ?M for the V617F mutation. The compound inhibits JAK2 kinase activity by binding to the STAT-5 binding domain or the allosteric site of JAK2. In JAK2V617F-positive leukemia cells, ON044580 suppresses proliferation and induces apoptosis in Imatinib-resistant chronic myeloid leukemia (CML) cells. It also inhibits both wild type and T315I mutant forms of the BCR-ABL kinase. ON044580 is used in research for myeloproliferative diseases characterized by abnormal JAK/STAT signaling.