生物活性
ENMD-2076选择性作用于Aurora A和VEGFR(Flt3)，IC50分别为14 nM和1.86 nM，作用于Aurora A比作用于Aurora B选择性高25倍，对VEGFR2/KDR和VEGFR3， FGFR1和FGFR2和PDGFRα作用效果稍弱。ENMD-2076有效作用于血管生成的多种激酶，包括VEGFR2/KDR 和VEGFR3, FGFR1和FGFR2, 及PDGFRα，IC50 为1.86到120 nM。ENMD-2076抑制多种人类实体瘤和血癌细胞系，IC50为0.025 到0.7μM, 诱导细胞凋亡，且使细胞周期停止在G2/M 期。ENMD-2076 作用于乳腺癌，结肠癌,黑色素瘤,白血病,多发性骨髓瘤细胞系移植瘤模型，诱导肿瘤衰退或完全抑制肿瘤生长。
化学数据
| 分子量 | 525.56 |
| 分子式 | C25H31N7O6 |
| CAS号 | 934353-76-1 |
| 纯度 | >99% |
| 溶解性（25°C） | DMSO |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | solid tumor cell lines and HUVECs, human leukemia cell lines |
| 方法 | Cell and proliferative assays
Cell lines were routinely tested for mycoplasma and used at low passage numbers (<10). The antiproliferative effect of ENMD-2076 on adherent tumor cell lines was measured by plating 500 cells per well in a 96-well plate and incubating with 9 doses of compound, spanning 0.3 nmol/L to 125 μmol/L, for 96 hours. Cellular proliferation was measured using the sulforhodamine B (SRB; Sigma Aldrich) assay (10). The leukemia-derived, nonadherent cell lines were assayed by plating 5,000 cells per well in a 96-well plate. The cells were incubated with 9 doses of compound, spanning 0.3 nmol/L to 125 μmol/L, for 48 hours and then survival was assayed using the Alamar Blue reagent (Invitrogen) according to the manufacturer’s instructions. To measure the effect of ENMD-2076 on VEGF- and fibroblast growth factor (FGF)-induced proliferation of human umbilical vein endothelial cell (HUVEC), cells were serum starved for 6 hours, then treated with ENMD-2076 free base, and stimulated with 5 ng/mL bFGF or 25 ng/mL VEGF (R and D Systems) for 72 hours. Cell proliferation was measured using WST-1 (Roche Applied Science) according to the manufacturer’s instructions. |
| 浓度 | 0.3 nM~125 μM |
| 处理时间 | 48 or 96 h |
| 动物实验 |
|---|
| 动物模型 | MDA-MB-231 tumor xenograft model of 5- to 6-week-old CB.17 SCID or NCr nude mice |
| 配制 | ENMD-2076 in water or ENMD-2076 free base in CMC-Tween vehicle (0.075% carboxymethylcellulose, 0.085% Tween 80 in water) |
| 剂量 | 75 or 302 mg/kg daily |
| 给药处理 | orally |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9027 mL | 9.5137 mL | 19.0273 mL |
| 5 mM | 0.3805 mL | 1.9027 mL | 3.8055 mL |
| 10 mM | 0.1903 mL | 0.9514 mL | 1.9027 mL |
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