AKI603

SKU: orb1685708

Description

AKI603 is a potent and selective Aurora kinase A (AurA) inhibitor with an IC50 of 12.3 nM. It was developed to target BCR-ABL-T315I mutation-driven resistance, demonstrating robust anti-proliferative effects in leukemic cell lines in vitro and showing potential for leukemia research.

Research Area

Cell Biology, Epigenetics & Chromatin

Key Properties

• CAS Number: 1432515-73-5
• MW: 409.45
• Purity: 99.81% (May vary between batches)
• Formula: C₁₉H₂₃N₉O₂
• SMILES: CN1CCN(CC1)c1cc(Nc2cc(C)[nH]n2)nc(Nc2ccc(cc2)[N+]([O-])=O)n1
• Target: Aurora Kinase
• Solubility: DMSO:120 mg/mL (293.08 mM)

Bioactivity

• Target IC50:
  Aurora A:12.3 nM
• In Vivo:
  AKI603 exhibits moderate oral bioavailability and Cmax following oral administration. AKI603 exhibits terminal elimination half-life following intravenous administration. AKI603 abrogates the growth of xenografted KBM5-T315I cells in nude mice.
• In Vitro:
  AKI603 inhibits the proliferation and colony formation of imatinib resistant CML cells. 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 as well as 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.
• Cell Research:
  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). 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.
• Animal Research:
  AKI603 (12.5-25 mg/kg; i.p.; every 2 days; for 14 days; female BALB/c nude mice with KBM5-T315I cells xenografted) abrogates the growth of tumors. Pharmacokinetic Analysis shows that AKI603 exhibits moderate oral bioavailability (rat 28.7%) and Cmax (rat 202.4 μg/L) following oral administration (rat 25 mg/kg). AKI603 also exhibits terminal elimination half-life (rat 8.9 h) following intravenous administration (rat 2.5 mg/kg).

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

imatinib-resistant, leukemia, Inhibitor, inhibit, myeloid, AKI 603, AKI603, AKI-603, Aurora A, AuroraKinase, Aurora Kinase, CML, chronic

Compound Identifiers

PubChem CID

72194397