生物活性
CP-547632是一种新型的、有效的血管内皮生长因子受体-2酪氨酸激酶抑制剂，用于癌症治疗。血管内皮生长因子(VEGF)受体信号通路是内皮细胞增殖和迁移的关键途径，从而导致血管生成，这是人类肿瘤生长和转移的必要条件。CP-547632被鉴定为VEGFR-2和碱性成纤维细胞生长因子(FGF)激酶的有效抑制剂(IC(50)分别为11和9 nM)。与表皮生长因子受体、血小板衍生生长因子β和其他相关的tk相比，它具有选择性。在全细胞实验中，CP-547632也抑制vegf刺激的VEGFR-2的自磷酸化，IC(50)值为6 nM。在NIH3T3/H-ras肿瘤小鼠口服CP-547632后，肿瘤中的VEGFR-2磷酸化受到剂量依赖性的抑制(EC(50) = 590 ng/ml)。CP-547632对紫杉醇和卡铂的药理学特征没有显著影响。在体内，CP-547632可有效抑制碱性FGF和vegf诱导的血管生成。CP-547632是一种耐受性良好的口服生物可利用抑制剂，目前正在临床研究用于人类恶性肿瘤的治疗。
化学数据
| 分子量 | 532.4 |
| 分子式 | C20H24BrF2N5O3S |
| CAS号 | 252003-65-9 |
| 纯度 | >98% |
| 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 | Porcine aortic endothelial cells |
| 方法 | Cells were seeded at 1.6 × 105cells/ml in 2-ml growth medium (Ham’s F-12 medium supplemented with 10% FBS, 50,000 units each penicillin and streptomycin, and 500 μg/ml gentamicin) per well in six-well plates. On day 2, the growth medium was replaced with serum-depleted medium (as above, but with 0.1% FBS and 0.1% BSA), and cells were incubated overnight. Immediately before compound addition, the medium was replaced with serum-depleted medium without BSA. Compounds were diluted in 100% DMSO, added to the cells at a final DMSO concentration of 0.25% v/v, and incubated at 37°C for 1 h. The cells were then stimulated with 500 ng/ml VEGF (Becton Dickinson, prepared in serum-depleted medium supplemented with 10 mm NaVO4) and incubated as above for an additional 8 min. The medium was removed and the cells washed once with PBS supplemented with 1 mm NaVO4, then lysed with 1 ml of immunoprecipitation assay buffer [10 mm Tris-HCl (pH 7.5), 50 mm NaCl, 25 mm EDTA, 1% NP40, 0.25% sodium deoxycholate, 2 mm NaVO4, and 1 EDTA-free complete protease inhibitor tablet per 25 ml]. Cell lysates were centrifuged at 14,000 rpm to pellet cellular debris, transferred to a new tube containing 4 μg anti-Flk-1 (Santa Cruz Biotechnology Laboratories; C20), and incubated with agitation overnight at 4°C. The antibody-protein complex was captured with protein A agarose beads (Santa Cruz Biotechnology Laboratories) for 30 min at 4°C and the protein boiled off in the presence of DTT. After electrophoresis and transfer to Immobilon-P membranes, the blots were probed with antibodies recognizing either the protein (monoclonal anti-Flk-1; Santa Cruz Biotechnology Laboratories; A3) or anti-PY-HRP. After incubation of the blot in enhanced chemiluminescence reagent (Amersham), bands were visualized on film or using the Lumi-ImagerF1 (Roche). |
| 浓度 | 0~10 μ M |
| 处理时间 | 1 h |
| 动物实验 |
|---|
| 动物模型 | athymic mice bearing Colo-205, DLD-1; and MDA-MB-231 cells tumour xenograft |
| 配制 | 5% Gelucire |
| 剂量 | 6.25–100 mg/kg qd. for 24 days |
| 给药处理 | oral gavage |
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 | 1.8783 mL | 9.3914 mL | 18.7829 mL |
| 5 mM | 0.3757 mL | 1.8783 mL | 3.7566 mL |
| 10 mM | 0.1878 mL | 0.9391 mL | 1.8783 mL |
m.cnreagent.com