Ilorasertib is a multi-kinase inhibitor.1 It inhibits Aurora C, VEGFR1, VEGFR2, FLT3, colony-stimulating factor 1 receptor (CSF1R), and Aurora B (IC50s = 1, 1, 2, 1, 3, and 7 nM, respectively). It also inhibits PDGFRα, PDGFRβ, c-Kit, VEGFR3, and Aurora A (IC50s = 11, 13, 20, 43, and 120 nM, respectively). Ilorasertib inhibits autophosphorylation of Aurora A, -B, and -C in HeLa cells with IC50 values of 189, 13, and 13 nM, respectively. It inhibits proliferation of a variety of cancer cells, including MV4-11 acute myeloid leukemia (AML), SUP-B15 acute lymphocytic leukemia (ALL), and H1299 non-small cell lung cancer (NSCLC) cells (IC50s = 0.3, 4, and 2 nM, respectively). It decreases histone H3 phosphorylation in blood-borne tumor cells in an engrafted mouse model of leukemia when administered at a dose of 25 mg/kg and reduces tumor growth in fibrosarcoma, pancreatic carcinoma, ALL, and multiple myeloma mouse xenograft models.
1.Glaser, K.B., Li, J., Marcotte, P.A., et al.Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase familiesJ. Pharmacol. Exp. Ther.343(3)617-627(2012)