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.

Product information

CAS Number: 1432515-73-5

Molecular Weight: 409.45

Formula: C19H23N9O2

Chemical Name: N4-(5-methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-N2-(4-nitrophenyl)pyrimidine-2,4-diamine

Smiles: CN1CCN(CC1)C1=CC(NC2C=C(C)NN=2)=NC(NC2C=CC(=CC=2)[N+]([O-])=O)=N1

InChiKey: UNKOUVAYOLLXER-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 125 mg/mL (305.29 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

AKI603 (0.039-0.6 μM; 48 hours) extensively inhibits proliferation of leukemia cells. 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. AKI603 inhibits the proliferation and colony formation of imatinib resistant CML cells. 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. Inhibition of AurA by AKI603 induces leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells. 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).

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. AKI603 exhibits moderate oral bioavailability (rat 28.7%) and Cmax (rat 202.4 μg/L) following oral administration (rat 25 mg/kg). AKI603 exhibits terminal elimination half-life (rat 8.9 h) following intravenous administration (rat 2.5 mg/kg).

Products are for research use only. Not for human use.