Zaurategrast
(Synonyms: N-(2-溴-3-氧代螺[3.5]壬-1-烯-1-基)-4-(2,7-萘啶-1-基氨基)-L-苯基丙氨酸,CT7758) 目录号 : GC37960
Zaurategrast (CT7758) 是一种口服有效的 α4-integrin 抑制剂。
Cas No.:455264-31-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[3]Male Wistar rats (250-320 g) and CD-1 mice (20-25 g), Non-naive male Beagle dogs weighing 10 kg, and non-naive male cynomolgus monkeys weighing 3 kg are used. For plasma pharmacokinetic studies, CT7758 is administered orally (5-10 mL/kg, 30 mg/kg) or intravenously (2 mL/kg, 3 mg/kg) as a solution in 10 mM phosphate buffer. CDP323 is administered orally as a 1% methylcellulose suspension containing 0.1% Tween 80 (same dosage volume as CT7758). Compounds are delivered to fasted animals with the food returned 4 hours postdose. Blood samples are collected at the designated time points. Plasma is prepared by centrifugation, collected, and stored at −20°C until analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). |
References: [1]. Wolf C, et al. Pharmacodynamic consequences of administration of VLA-4 antagonist CDP323 to multiple sclerosis subjects: a randomized, double-blind phase 1/2 study. PLoS One. 2013;8(3):e58438. | |
Zaurategrast (CT7758) is a potent and oral-effective α4-integrin inhibitor. α4-integrin[1]
CDP323 is an ethyl ester prodrug of CT7758, a potent carboxylic acid antagonist of α4β1 (very late antigen-4, VLA-4) and, to a lesser extent, α4β7 integrins. CDP323 is developed as a VLA-4 antagonist prodrug for the treatment of multiple sclerosis[2].
CDP323 is a potent and effective α4 inhibitor that is well tolerated at oral doses up to 1000 mg twice daily (bid). Relative to placebo, all dosages of Zaurategrast (CDP-323) significantly decreased the capacity of lymphocytes to bind vascular adhesion molecule-1 (VCAM-1) and the expression of α4-integrin on VCAM-1-binding cells. CDP323 at daily doses of 1000 or 2000 mg induced significant increases in total lymphocyte count and suppressed VCAM-1 binding by reducing unbound very late antigen-4 expression on lymphocytes[1]. After oral administration of CDP323, CT7758 is by far the most abundant circulating plasma component, peaking between 0.5 and 1.5 hours irrespective of the species. These data suggested that CDP323 is rapidly absorbed and efficiently hydrolyzed into CT7758. Plasma exposure of CT7758 showed a large species variability with dog>rat=mice>cynomolgus monkey. In the tested dose range of 25-50 mg/kg, the estimated oral bioavailability (i.e., based on intravenous administration of CT7758 and assuming linear PK) is 29, 27, 8, and 0.3% in mice, rat, dog, and cynomolgus monkey, respectively. CDP323 increased the absorption of CT7758 by 5- to 10-fold in rodents, whereas no significant increase is observed in dog and monkey[3].
[1]. Wolf C, et al. Pharmacodynamic consequences of administration of VLA-4 antagonist CDP323 to multiple sclerosis subjects: a randomized, double-blind phase 1/2 study. PLoS One. 2013;8(3):e58438. [2]. Chanteux H, et al. In Vitro Hydrolysis and Transesterification of CDP323, an α4β1/α4β7 Integrin Antagonist Ester Prodrug. Drug Metab Dispos. 2014 Jan;42(1):153-61. [3]. Chanteux H, et al. Cross-Species Differences in the Preclinical Pharmacokinetics of CT7758, an α4β1/α4β7 Integrin Antagonist. Drug Metab Dispos. 2015 Sep;43(9):1381-91.
| Cas No. | 455264-31-0 | SDF | |
| 别名 | N-(2-溴-3-氧代螺[3.5]壬-1-烯-1-基)-4-(2,7-萘啶-1-基氨基)-L-苯基丙氨酸,CT7758 | ||
| Canonical SMILES | O=C1C(Br)=C(C12CCCCC2)N[C@H](C(O)=O)CC3=CC=C(NC4=NC=CC5=CC=NC=C45)C=C3 | ||
| 分子式 | C26H25BrN4O3 | 分子量 | 521.41 |
| 溶解度 | DMSO: 100 mg/mL (191.79 mM) | 储存条件 | Store at -20°C |
| General tips | 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。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9179 mL | 9.5894 mL | 19.1788 mL |
| 5 mM | 0.3836 mL | 1.9179 mL | 3.8358 mL |
| 10 mM | 0.1918 mL | 0.9589 mL | 1.9179 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。