体外研究
(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].
Cell Proliferation Assay[1] | Cell Line: | U937 cells, HL-60 cells, NB4 cells, KBM5 cells, K562 cells, Jurkat cells | | Concentration: | 0.039 μM, 0.078 μM, 0.16 μM, 0.3 μM, 0.6 μM | | Incubation Time: | 48 hours | | Result: | Inhibited all the tested cell lines. |
Western Blot Analysis[1] | Cell Line: | NB4 cells, K562 cells, Jurkat cells | | Concentration: | 0.039 μM, 0.078 μM, 0.16 μM, 0.3 μM, 0.6 μM | | Incubation Time: | 48 hours | | Result: | Inhibited the phosphorylation of AurA Thr288 (p-AurA). |
Cell Cycle Analysis[1] | Cell Line: | K562, K562/G, 32D-p210 and 32D-T315I cells | | Concentration: | 0.3 μM, 0.6 μM | | Incubation Time: | 48 hours | | Result: | Induced polyploidization in the tested cells. |
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体内研究
(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 Cmax(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].
| Animal Model: | Female BALB/c nude mice, with KBM5-T315I cells xenografted[1] | | Dosage: | 12.5 mg/kg, 25 mg/kg | | Administration: | Intraperitoneal injection, every 2 days, for 14 days | | Result: | Significantly inhibited the growth of tumors. |
| Animal Model: | SD rats (220-280 g)[3] | | Dosage: | 2.5 mg/kg for i.v.; 25 mg/kg for p.o. (Pharmacokinetic Analysis) | | Administration: | Intravenous injection, oral administration | | Result: | Oral bioavailability (28.7%), Cmax(202.4 μg/L), T1/2(8.9 h) |
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