Reversine

Reversine is a novel class of ATP-competitive Aurora kinase inhibitor with IC₅₀s of 400, 500 and 400 nM for Aurora A, Aurora B and Aurora C, respectively. IC50 & Target: IC50: 400 nM (Aurora Kinase A), 500 nM (Aurora Kinase B), 400 nM (Aurora Kinase C)^[1] In Vitro: Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells. Reversine is a potent inhibitor of Aurora A and B and is also an inhibitor of Aurora C kinase. Aurora A and B activities are inhibited by 80% and Aurora kinase C by 55%, already at a concentration of 0.5 μM, whereas no inhibition or only modest inhibition is observed on others kinases tested. In a second round of experiments, the IC₅₀ of Reversine is determined on Aurora kinase A to be 400 nM, whereas Aurora kinase B and C IC₅₀ are 500 and 400 nM, respectively. The IC₅₀ is also determined on MEK1 is >1.5 μM and that the IC₅₀ on muscle myosin (an analogue of nonmuscle myosin II) is 350 nM^[1]. In Vivo: The combination of Reversine and aspirin can more efficiently induce cell cycle arrest and apoptosis. To evaluate the anti-tumor effect of this combination, a xenograft nude mouse model is established by s.c. injection. Mice inoculated with cervical cancer cells have lost about 10 % of their initial body weight by about 16 days after tumor inoculation. However, tumor growth (tumor weight) is reduced and the mice survive longer in the combination group^[2].