AKI603, an Aurora kinase A (AurA) inhibitor with an IC50 of 12.3 nM, is designed to counteract resistance from the BCR-ABL-T315I mutation. It demonstrates potent anti-proliferative effects in leukemic cells[1][2].
体内研究
AKI603 (12.5-25 mg/kg; i.p.; every 2 days; for 14 days) eliminates the growth of KBM5-T315I xenografts in nude mice[1].
Following oral administration in rats (25 mg/kg), AKI603 demonstrates moderate oral bioavailability (28.7%) and a peak concentration (Cmax) of 202.4 μg/L[3].
After intravenous administration in rats (2.5 mg/kg), AKI603 has a terminal elimination half-life of 8.9 hours[3].
体外研究
AKI603 (0.039-0.6 μM; 48 hours) greatly suppresses the growth of leukemia cells[1].
AKI603 (0.039-0.6 μM; 48 hours) markedly reduces AurA phosphorylation in NB4, K562, and Jurkat cells in a dose-dependent way without altering total AurA protein levels[1].
AKI603 hampers both the growth and colony-forming ability of imatinib-resistant CML cells[1].
AKI603 (0.3-0.6 μM; 48 hours) reduces cell growth and the ability to form colonies in imatinib-resistant CML cells by triggering cell cycle arrest and polyploidy accumulation[1].
Inhibition of AURA by AKI603 induces the bleaching of the BCR-ABL cell regulator in wild-type and T315I mutant cells [1].
AKI603 shows effectiveness in inhibiting the proliferation of breast cancer cells, with IC50 values as follows: SUM149 (2.04), BT549 (0.86), MCF-7 (0.97), MCF-7-Epi (21.01), Sk-br-3 (0.73), MDA-MB-231 (3.49), MDA-MB-453 (MTT, 0.18; Cell counting, 0.19), MDA-MB-468 (MTT, 0.15; Cell counting, 0.17)[2].
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