AuroraB/VEGFr/FGFR inhibitor AL8326

An orally bioavailable inhibitor of the receptor kinases Aurora B, fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor receptor (VEGFR), with potential antimitotic, antiangiogenic and antineoplastic activities. Upon oral administration, Aurora B/VEGFR/FGFR inhibitor AL8326 specifically binds to and inhibits the activity of Aurora B, FGFR and VEGFR. Inhibition of Aurora B causes disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, inhibition of cell division and the induction of apoptosis in cells overexpressing Aurora B. Inhibition of FGFR and VEGFR prevents the activation of their downstream signaling pathways and the proliferation of tumor cells overexpressing these kinases. FGFR and VEGFR are upregulated in a variety of cancer cell types and play key roles in tumor cell proliferation, angiogenesis, and metastasis. Aurora B is a positive regulator of mitosis that plays a key role in the attachment of the mitotic spindle to the centromere; the segregation of sister chromatids to each daughter cell; and the separation of daughter cells during cytokinesis. This serine/threonine kinase may be amplified and overexpressed by a variety of cancer cell types.