Description

• A cell-permeable indazolylimidazopyridazinamine compound that acts as a potent and reversible inhibitor of histone kinase haspin activity (IC 50 = 2nM) with moderate selectivity over TrkA, GSK-3β, PIM1, Cdk1/B and Cdk2/A (% inhibition at 100nM = 58, 48, 36, 34 and 33, respectively) among a panel of 27-kinases
• Shown to block pH3-Thr 3 , with no effect on pH3-Ser 10 and pH3-Ser 28 , cause mitotic catastrophe, upregulate BUB1 and cyclin B1 levels, and potently induce apoptosis (IC 50 = 473, 500 and 752nM in HeLa, HCT-116 and MDA-MB-231 cells, respectively)
• Further, efficiently blocks bFGF-induced sprouting vessel by 70% at 1μM (chicken embryo aortic arch ring assay) and suppresses tumor growth in HCT-116 xenografted mouse model (50mg/kg, i.p.).