Substance
ID:73347
Names and Identifiers
IUPAC name
N-(2-chlorophenyl)-4-{[2-({4-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]phenyl}amino)-5-fluoropyrimidin-4-yl]amino}benzamide
IUPAC Traditional name
N-(2-chlorophenyl)-4-{[2-({4-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]phenyl}amino)-5-fluoropyrimidin-4-yl]amino}benzamide
Synonyms
Aurora A Inhibitor I
Registration numbers
CAS Number
Properties
Safety Information
Storage Condition
-20°C
Product Information
Salt Data
Free Base
Physical Property
Solubility
DMSO
Pharmacology Properties
Target
Aurora Kinase
Molecule Details
Research Area
Description
Cancer
Biological Activity
Description
Aurora A Inhibitor I is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM.
Targets
Aurora A
IC50
3.4 nM
In Vitro
Aurora A Inhibitor I is a 2,4-dianilinopyrimidine that selectively and potently inhibits Aurora A. Aurora A Inhibitor I effectively inhibits the proliferation of HCT116 and HT29 cells, with IC50 of 190 nM and 2.9 μM, respectively. The Aurora A selectivity of Aurora A Inhibitor I against Aurora B depends on a single amino acid (Thr217) of Aurora A. [1] In KCL-22 cells, Aurora A Inhibitor I (1–5 μM) increases G2/M cell fraction, induces histone H3 serine 10 phosphorylation, and suppresses mitotic Aurora A autophosphorylation on Thr288. Aurora A Inhibitor I (0.5–5 μM) also suppresses cell proliferation in KCL-22 cells, as well as BCR-ABL-negative leukemia cell lines KG-1 and HL-60. Aurora A Inhibitor I effectively induces apoptosis in KCL-22 cells at 5 μM. [2] In a recent study, Aurora A Inhibitor I is also found to inhibit cell growth of HCT116, HT29, and HeLa cells, with IC50 of 377.6 nM, 5.6 μM, and 416 nM. [3]
In Vivo
Clinical Trials
Features
Aurora A Inhibitor I is a novel, potent, and selective inhibitor to Aurora A.
Protocol
Kinase Assay [1]
Auroras A and B Inhibition Assays
Both Auroras A and B are assayed in ELISA format using a GST fusion (pGEX-4T) of the N-terminus of Histone H3 (aa 1?18) as substrate. Plates are coated with 2 μg/mL substrate in PBS then blocked with 1 mg/mL I-block in PBS. Kinase reactions are run for 40 min with 5 ng/mL (0.16 nM) Aurora A or 45 ng/mL (1.1 nM) Aurora B at 30 μM ATP (~ Km) in kinase buffer. Final DMSO concentration is 4%. Product is detected by incubation with antiphosphohistone H3 (Ser10) 6G3 mouse monoclonal antibody and sheep-anti-mouse HRP conjugate, followed by washing and addition of TMB substrate. After quenching with 1 M phosphoric acid, plates are read at 450 nM.
Cell Assay [1]
Cell Lines
HCT116 and HT29 cells
Concentrations
0.1 nM - 10 μM, dissolved in medium lacking serum and glutamine (dissolved in DMSO as stock solution)
Incubation Time
72 hours
Methods
Cells are seeded in 384-well plates on day 0 in 50 μL of complete medium and incubated overnight in a 5% CO2 atmosphere at 37 °C. On day 1, 10 μL of Aurora A Inhibitor I is added. On day 4, plates are allowed to reach room temperature, and 30 μL Cell Titer-Glo reagent is added to each well to measure total ATP levels. Plates are read after shaking 15 min at room temperature.
Animal Study []
Molecular Spectra
No Data Available
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References
• Rawson TE, et al. J Med Chem, 2008, 51(15), 4465-4475.
• Kwiatkowski N, et al. ACS Chem Biol, 2012, 7(1), 185-196.
• Yuan H, et al. Carcinogenesis, 2012, 33(2), 285-293.
• Aliagas-Martin I, et al. J Med Chem, 2009, 52(10), 3300-3307.