AKI603

AKI603 is an inhibitor of Aurora kinase A (AurA), with an IC₅₀ of 12.3 nM. AKI603 is developed to overcome resistance mediated by BCR-ABL-T315I mutation. AKI603 exhibits strong anti-proliferative activity in leukemic cells^[1][2]. IC50 & Target: AurA^[1] In Vitro: AKI603 (0.039-0.6 μM; 48 hours) extensively inhibits proliferation of leukemia cells^[1].
AKI603 (0.039-0.6 μM; 48 hours) significantly inhibits the phosphorylation of AurA in NB4, K562, and Jurkat cell lines in a dose-dependent manner while the level of total AurA protein is not changed^[1].
AKI603 inhibits the proliferation and colony formation of imatinib resistant CML cells^[1].
AKI603 (0.3-0.6 μM; 48 hours) inhibits cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation^[1].
Inhibition of AurA by AKI603 induces leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells^[1].
AKI603 exhibits inhibitory activities on breast cancer cell proliferation, such as SUM149 (IC₅₀=2.04), BT549 (IC₅₀=0.86), MCF-7 (IC₅₀=0.97), MCF-7-Epi (IC₅₀=21.01), Sk-br-3 (IC₅₀=0.73), MDA-MB-231 (IC₅₀=3.49), MDA-MB-453 (MTT, IC₅₀=0.18; Cell counting, IC₅₀=0.19), MDA-MB-468 (MTT, IC₅₀=0.15; Cell counting, IC₅₀=0.17)^[2].
In Vivo: AKI603 (12.5-25?mg/kg; i.p.; every 2 days; for 14 days) abrogates the growth of xenografted KBM5-T315I cells in nude mice^[1].
AKI603 exhibits moderate oral bioavailability (rat 28.7%) and C_max (rat 202.4 μg/L) following oral administration (rat 25 mg/kg)^[3].
AKI603 exhibits terminal elimination half-life (rat 8.9 h) following intravenous administration (rat 2.5 mg/kg)^[3].