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ON044580, an α-benzoyl styryl benzyl sulfide, is a potent and non-ATP-competitive JAK2 kinase inhibitor with IC50s 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 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[1]. | [IC 50]
JAK2-WT: 1.23 μM (IC50); JAK2-V617F: 1.09 μM (IC50); WT BCR-ABL; T315I-BCR-ABL | [References]
[1] Shashidhar S Jatiani, et al. A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition. Genes Cancer. 2010 Apr;1(4):331-45. DOI:10.1177/1947601910371337 |
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