| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Aurora A (IC50 = 12.3 nM)
AKI603 targets Aurora A kinase [1] AKI603 targets Aurora A kinase and Aurora B kinase [2] |
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| ln Vitro |
AKI603 (0.039-0.6 μM; 48 hours) significantly reduces leukemia cell division[1].
AKI603 (0.039-0.6 μM; 48 hours) has a dose-dependent effect on the phosphorylation of AurA in the NB4, K562, and Jurkat cell lines, but has no effect on the amount of total AurA protein[1]. AKI603 suppresses the growth and colony formation of CML cells resistant to imatinib[1]. AKI603 (0.3-0.6 μM; 48 hours) induces cell cycle arrest with polyploidy accumulation in imatinib-resistant CML cells, inhibiting their ability to proliferate and form colonies[1]. AKI603-induced inhibition of AurA causes leukemia cell senescence in 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 chronic myeloid leukemia (CML) cells harboring T315I mutation (K562-T315I, MEG-01-T315I), AKI603 inhibited cell proliferation, induced cellular senescence (evidenced by increased senescence-associated β-galactosidase (SA-β-gal) activity), upregulated senescence markers p21 and p16 (detected by western blot), and suppressed colony formation [1] In breast cancer cells and breast tumor-initiating cells (BTICs), AKI603 inhibited cell proliferation, reduced the proportion of CD44+/CD24- BTICs (flow cytometry), downregulated stemness-related genes (Oct4, Sox2, Nanog) via PCR, and overcame paclitaxel resistance by inhibiting Aurora kinase-mediated signaling [2] |
| ln Vivo |
AKI603 (12.5–25 mg/kg; intraperitoneally; every 2 days; for 14 days) prevents xenografted KBM5–T315I cells from growing in nude mice.[1]
AKI603 shows a moderate oral bioavailability (rat 28.7%) and a Cmax of 202.4 μg/L after oral administration (rat 25 mg/kg)[3]. AKI603 has a terminal elimination half-life of 8.9 hours (rat 2.5 mg/kg) after intravenous administration[3]. In nude mice bearing breast cancer xenografts, AKI603 significantly inhibited tumor growth, reduced tumor weight, and decreased BTIC frequency in tumors compared to controls [2] |
| Enzyme Assay |
Recombinant Aurora A kinase was incubated with specific substrate, ATP, and various AKI603 concentrations in reaction buffer. After 37°C incubation, substrate phosphorylation was detected by luminescent assay, and IC50 was calculated based on inhibition rate [1]
Recombinant Aurora A/B kinases were used to evaluate AKI603 activity. The reaction system included kinase, substrate peptide, ATP, and AKI603 (different concentrations). Phosphorylated substrate was quantified by colorimetric assay to determine IC50 for Aurora A and B [2] |
| Cell Assay |
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. CML cells (K562-T315I, MEG-01-T315I) were seeded in 96-well plates and treated with 0.1-10 μM AKI603 for 72 hours; cell viability was assessed by cell counting kit to calculate IC50. Cells treated with AKI603 for 48 hours were fixed and stained with SA-β-gal to count senescent cells. Western blot detected p21, p16, Aurora A, and phosphorylated histone H3 (pH3). For colony formation, cells were treated with AKI603 for 24 hours, seeded in 6-well plates, cultured for 14 days, then stained and counted [1] Breast cancer cells were cultured, and BTICs were isolated by CD44+/CD24- magnetic sorting. BTICs and parental cells were treated with AKI603 for 72 hours; proliferation was measured by MTT assay. Flow cytometry analyzed CD44+/CD24- proportion. PCR detected stemness gene mRNA, and western blot examined Aurora A, pH3, and cleaved caspase-3 [2] |
| Animal Protocol |
Female BALB/c nude mice, with KBM5-T315I cells xenografted[1]
12.5 mg/kg, 25 mg/kg Intraperitoneal injection, every 2 days, for 14 days 6-8 week-old nude mice were subcutaneously injected with breast cancer cells to establish xenografts. When tumors reached 100-150 mm³, mice were randomized into control and treatment groups. AKI603 was dissolved in solvent and administered intraperitoneally at a specified dose every other day for 2 weeks. Tumor volume was measured every 3 days; mice were euthanized to collect tumors for analysis [2] 200-250 g Sprague-Dawley rats were assigned to oral and intravenous groups. Intravenous group received 5 mg/kg AKI603 via tail vein; oral group received 20 mg/kg AKI603 by gavage. Blood samples were collected at 0, 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours, centrifuged for plasma, and AKI603 concentrations were detected by UPLC-MS/MS [3] |
| ADME/Pharmacokinetics |
After intravenous injection of 5 mg/kg AKI603 in rats, key pharmacokinetic parameters included AUC0-∞, t1/2 and Vd. After oral administration of 20 mg/kg AKI603, Cmax, Tmax, AUC0-∞, t1/2 and oral bioavailability (F) were calculated [3].
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| References |
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| Additional Infomation |
AKI603 is a novel small-molecule Aurora kinase inhibitor with potential therapeutic effects against drug-resistant tumors (T315I-mutant chronic myeloid leukemia and paclitaxel-resistant breast cancer) [1,2]. AKI603 exerts its antitumor effects by inhibiting Aurora kinase activity, inducing senescence in chronic myeloid leukemia cells, and inhibiting BTIC stemness [1,2].
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| Molecular Formula |
C19H23N9O2
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|---|---|
| Molecular Weight |
409.445021867752
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| Exact Mass |
409.197
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| Elemental Analysis |
C, 55.73; H, 5.66; N, 30.79; O, 7.81
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| CAS # |
1432515-73-5
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| Related CAS # |
1432515-73-5
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| PubChem CID |
72194397
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| Appearance |
White to yellow solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
561
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UNKOUVAYOLLXER-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23N9O2/c1-13-11-17(25-24-13)21-16-12-18(27-9-7-26(2)8-10-27)23-19(22-16)20-14-3-5-15(6-4-14)28(29)30/h3-6,11-12H,7-10H2,1-2H3,(H3,20,21,22,23,24,25)
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| Chemical Name |
6-(4-methylpiperazin-1-yl)-4-N-(5-methyl-1H-pyrazol-3-yl)-2-N-(4-nitrophenyl)pyrimidine-2,4-diamine
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| Synonyms |
AKI-603; AKI603; AKI 603
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 82~16.125 mg/mL (200.3~305.3 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 6.25 mg/mL (15.26 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4423 mL | 12.2115 mL | 24.4230 mL | |
| 5 mM | 0.4885 mL | 2.4423 mL | 4.8846 mL | |
| 10 mM | 0.2442 mL | 1.2212 mL | 2.4423 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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