Hesperadin

Hesperadin is an inhibitor of human Aurora B, prevented the phosphorylation of substrate with IC50 of 40 nM. Hesperadin significantly inhibits cell growth of cultured bloodstream forms with IC50 of 50 nM. Hesperadin also inhibits the ability of immunoprecipitated Aurora B to phosphorylate histone H3 with IC50 of 250 nM and markedly reduces the activity of other kinases (AMPK, Lck, MKK1, MAPKAP-K1, CHK1 and PHK) at a concentration of 1 μM. Hesperadin blocked nuclear division and cytokinesis but not other aspects of the cell cycle. Molecular models predicted high-affinity binding of Hesperadin to both conserved and novel sites in TbAUK1. Hesperadin treatment causes defects in mitosis and cytokinesis, leading to stoppage of proliferation of HeLa cells and polyploidization.