N-(2-chlorophenyl)-4-{[2-({4-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]phenyl}amino)-5-fluoropyrimidin-4-yl]amino}benzamide

• ChemBase编号: 72684
• 分子式: C31H31ClFN7O2
• 平均质量: 588.0749432
• 单一同位素质量: 587.22117917
• SMILES: n1cc(c(nc1Nc1ccc(cc1)CC(=O)N1CCN(CC1)CC)Nc1ccc(cc1)C(=O)Nc1ccccc1Cl)F
• Canonical SMILES: CCN1CCN(CC1)C(=O)Cc1ccc(cc1)Nc1ncc(c(n1)Nc1ccc(cc1)C(=O)Nc1ccccc1Cl)F
• InChI: InChI=1S/C31H31ClFN7O2/c1-2-39-15-17-40(18-16-39)28(41)19-21-7-11-24(12-8-21)36-31-34-20-26(33)29(38-31)35-23-13-9-22(10-14-23)30(42)37-27-6-4-3-5-25(27)32/h3-14,20H,2,15-19H2,1H3,(H,37,42)(H2,34,35,36,38)
• InChIKey: AKSIZPIFQAYJGF-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: N-(2-chlorophenyl)-4-{[2-({4-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]phenyl}amino)-5-fluoropyrimidin-4-yl]amino}benzamide
• IUPAC传统名: N-(2-chlorophenyl)-4-{[2-({4-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]phenyl}amino)-5-fluoropyrimidin-4-yl]amino}benzamide
• 别名: Aurora A Inhibitor I

登记号

• CAS号: 1158838-45-9
• PubChem SID: 162037605
• PubChem CID: 44139710

理论计算性质

• Acid pKa: 11.155244
• 质子受体: 7
• 质子供体: 3
• LogD (pH = 5.5): 3.6507204
• LogD (pH = 7.4): 5.235142
• Log P: 5.523547
• 摩尔折射率: 164.2308 cm^3
• 极化性: 60.899303 Å^3
• 极化表面积: 102.49 Å^2
• 可自由旋转的化学键: 9
• 里宾斯基五规则: false

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Aurora Kinase

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1451

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; Aurora B; Aurora C
• IC50: 3.4 nM; 3.4 μM ^[1]; 0.432 μM ^[2]
• 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]
• Features: Aurora A Inhibitor I is a novel, potent, and selective inhibitor to Aurora A.

Protocol

• 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 (~ K_m) 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.
• Protocol: 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.

References

• References: [1] Aliagas-Martin I, et al. J Med Chem, 2009, 52(10), 3300-3307.
• References: [2] Yuan H, et al. Carcinogenesis, 2012, 33(2), 285-293.
• References: [3] Kwiatkowski N, et al. ACS Chem Biol, 2012, 7(1), 185-196.
• References: [4] Rawson TE, et al. J Med Chem, 2008, 51(15), 4465-4475.

参考文献

• Aliagas-Martin I, et al. J Med Chem, 2009, 52(10), 3300-3307.
• Yuan H, et al. Carcinogenesis, 2012, 33(2), 285-293.
• Kwiatkowski N, et al. ACS Chem Biol, 2012, 7(1), 185-196.
• Rawson TE, et al. J Med Chem, 2008, 51(15), 4465-4475.