| 中文名称: | 奥瑞布林盐酸盐 | ||||
|---|---|---|---|---|---|
| 英文名称: | Ombrabulin hydrochloride | ||||
| 别名: | 奥瑞布林盐酸盐 AVE8062 hydrochloride; AC7700 hydrochloride | ||||
| CAS No: | 253426-24-3 | 分子式: | C21H26N2O6.HCl | 分子量: | 438.9 |
| CAS No: | 253426-24-3 | ||||
| 分子式: | C21H26N2O6.HCl | ||||
| 分子量: | 438.9 | ||||
基本信息
|
产品编号：O10227 |
|||||
|
产品名称：Ombrabulin hydrochloride |
|||||
|
CAS: |
253426-24-3 |
储存条件 |
粉末 |
-20℃ |
四年 |
|
|
|
||||
|
分子式： |
溶于液体 |
-80℃ |
六个月 |
||
|
分子量 |
438.90 |
-20℃ |
一个月 |
||
|
化学名： |
|
||||
|
Solubility (25°C) |
体外 |
DMSO |
|
||
|
Ethanol |
|
||||
|
Water |
|
||||
|
体内（现配现用） |
|
|
|||
|
＜1mg/ml表示微溶或不溶。 |
|||||
|
普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
|||||
|
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 |
|||||
制备储备液
|
浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
|
1mM |
2.2784mL |
11.3921mL |
22.7842mL |
|
5mM |
0.4557mL |
2.2784mL |
4.5568mL |
|
10mM |
0.2278mL |
1.1392mL |
2.2784mL |
生物活性
|
产品描述 |
CA-4 磷酸酯的衍生物，选择性破坏内皮细胞的微管蛋白细胞骨架，具有抗血管作用。 |
|
靶点/IC50 |
tubulin |
|
体外研究 |
The effect of Ombrabulin (AVE8062) on endothelial or tumor cell viability is examined using the MTT assay. The IC50 of Ombrabulin for the mouse mesenteric endothelial cells (MMEC) is 10nM and ranges between 7 and 20nM for the tumor cell lines (HeyA8, SKOV3ip1, and HeyA8-MDR).Comparative analysis of the nonlinear least-squares regression of the doseresponse curves for each agent alone and combination Ombrabulin /Docetaxel show a significantly lower IC50 than either agent alone (P<0.005, all cell lines). The cytotoxicity of Docetaxel is 2- to 4-fold greater in combination with Ombrabulin for the endothelial and tumor cells compared with Docetaxel alone. |
|
体内研究 |
Before performing therapy experiments, the tolerability of various doses of Ombrabulin (AVE8062) ranging from 10 to 100mg/kg is tested given twice weekly via i.v., i.p., or s.c. routes in nude mice (n=3 per group). The i.v. and s.c. routes are not pursued further due to problems with skin or tail vein necrosis. The i.p. route is well tolerated with doses up to 100mg/kg.Next, preliminary experiments are done to determine the lowest dose for in vivo therapeutic efficacy. Starting 7 days after tumor cell injection, nude mice (n=5 per group) bearing HeyA8 ovarian cancer cells are treated with either vehicle or Ombrabulin 10, 30, 50, and 100mg/kg twice weekly i.p. for 3 weeks.There is 65% reduction in tumor weight in the 30 mg/kg group compared with the vehicle control group (P<0.02). The 10mg/kg dose is not effective. The antitumor effects at doses>30mg/kg are not significantly better;therefore, the 30 mg/kg dose is selected for subsequent therapy experiments. |
推荐实验方法(仅供参考)
|
细胞实验: |
|
|
The capacity of Ombrabulin (AVE8062) to modulate MMEC and HeyA8 cell cycle as well as apoptosis is analyzed by flow cytometry. In all assays, 3×106 tumor cells are seeded into Petri dishes and allowed to adhere overnight. The cultures are then washed with PBS and treated with regular medium (negative control) or medium containing Docetaxel, Ombrabulin (HeyA8,20nM;MMEC 10nM), or Ombrabulin plus Docetaxel. For cell cycle analyses, tumor cells are collected by trypsinization and pooled with the cells floating in the medium. The cell suspensions are centrifuged for 5 min at 1,500 rpm at room temperature, then washed and fixed with ethanol.For apoptosis analysis, cells are incubated overnight in 50μL of DNA labeling solution (10μL of reaction buffer, 0.75μL of TdT enzyme, 8μL of FITC-dUTP, and 32.25μL of distilled water) at room temperature. Following the addition of rinse buffer, samples are centrifuged, washed, and fixed in ethanol. All samples are then washed with PBS, then resuspended in propidium iodide (50μg/mL) and RNase A (20μg/mL) in PBS for 30 min at room temperature. Stained cells are analyzed on an EPICS XL flow cytometer. The low-level gate is set at the base of the G1 peak and the percentages of cells within the G1 and G2-M phases of the cell cycle are determined by analysis with Multicycle. |
|
|
动物实验: |
|
|
Mice Female athymic nude mice (6-8 weeks old) are used. For in vivo injection, tumor cells are trypsinized, centrifuged at 1,000 rpm×7 min at 4℃, washed twice, and resuspended in serum-free HBSS at a concentration of 5×106 cells/mL (SKOV3ip1 and HeyA8-MDR) and 1.25×106 cells/mL (HeyA8). Tumors are established by i.p. injection of cells. Ombrabulin therapy is initiated 7 or 17 days after cell line injection. Mice (n=10 per group) are randomly assigned to the following treatment groups: (a) PBS 200μL, i.p. weekly; (b) Ombrabulin 30mg/kg [dissolved in PBS (pH 5)] i.p. twice weekly; (c) Docetaxel 2mg/kg (HeyA8 and HeyA8-MDR) or 1.4mg/kg (SKOV3ip1) i.p. weekly; (d) Ombrabulin plus Docetaxel (both drugs given at the doses and frequency described above for each drug alone). The dose of Ombrabulin used in these experiments is optimized from doseescalation studies against tumor growth. Mice are monitored for signs of adverse effects and tumors are harvested after treatment (range 2-5 weeks). The mouse weight, tumor weight,number of tumor nodules, and volume of ascites are recorded at necropsy. |
|
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
