|
|
| | AKI-603
(AKI603) Basic information |
| Product Name: | AKI-603
(AKI603) | | Synonyms: | AKI-603
(AKI603);AKI-603;AKI603,Aurora Kinase,chronic,CML,leukemia,myeloid,inhibit,imatinib-resistant,Inhibitor;2,4-Pyrimidinediamine, 6-(4-methyl-1-piperazinyl)-N4-(5-methyl-1H-pyrazol-3-yl)-N2-(4-nitrophenyl)-;N4-(5-Methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-N2-(4-nitrophenyl)pyrimidine-2,4-diamine | | CAS: | 1432515-73-5 | | MF: | C19H23N9O2 | | MW: | 409.45 | | EINECS: | | | Product Categories: | | | Mol File: | 1432515-73-5.mol |  |
| | AKI-603
(AKI603) Chemical Properties |
| Boiling point | 710.2±70.0 °C(Predicted) | | density | 1.407±0.06 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMSO : 125 mg/mL (305.29 mM; Need ultrasonic) | | form | Solid | | pka | 14.19±0.10(Predicted) | | color | White to yellow |
| | AKI-603
(AKI603) Usage And Synthesis |
| Biological Activity | 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].
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].
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]. | | References | [1]. Le-Xun Wang, et al. Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation. Sci Rep. 2016 Nov 8;6:35533. [2]. Fei-Meng Zheng, et al. A novel small molecule aurora kinase inhibitor attenuates breast tumor-initiating cells and overcomes drug resistance. Mol Cancer Ther. 2014 Aug;13(8):1991-2003. [3]. Zhenzhen Zhao, et al. Determination of a novel Aurora-A (AurA) kinase AKI603 by UPLC-MS/MS and its application to a bioavailability study in rat. J Pharm Biomed Anal. 2016 Jun 5;125:303-9. |
| | AKI-603
(AKI603) Preparation Products And Raw materials |
|