The Aurora kinases (A, B, and C) are a family of serine-threonine kinases that regulate various stages of mitotic function. With significant roles in cell cycle and cell division, Aurora kinase gene amplification and overexpression are linked to tumorigenesis. MK-0457 is a potent pan-Aurora kinase inhibitor but favors Aurora A (Ki = 0.6 nM) over Aurora B (Ki = 18 nM) or Aurora C (Ki = 4.6 nM). It shows selectivity against a panel of more than 190 different protein kinases. MK-0457 effectively inhibits proliferation of several different cell lines of clear cell renal carcinoma (IC50s = <10 μM) and blocks the growth of tumors in a rodent model of cancer (80 mg/kg), inhibiting histone H3 phosphorylation and increasing apoptosis. By depleting Aurora activity, MK-0457 disrupts bipolar spindle formation during mitosis, arresting cell cycle progression at the G2/M phase.
