Napsagatran hydrate (Ro 46-6240 hydrate)
(Synonyms: 奈沙加群,Ro 46-6240 hydrate; Ro 46-6240/010 hydrate) 目录号 : GC34032
Napsagatran hydrate (Ro 46-6240 hydrate) 是一种新型的特异性凝血酶抑制剂。
Cas No.:159668-20-9
Sample solution is provided at 25 µL, 10mM.
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Napsagatran hydrate is a novel and specific thrombin inhibitor.
Napsagatran (Ro 46-6240), the selective thrombin inhibitor, induces a dose-dependent prolongation of the activated partial thromboplastin time (aPTT) and prothrombin time (PT) that is evident 15 min after administration of the bolus of Napsagatran. Napsagatran also reduces the time to reperfusion in a dose-dependent manner and delays or prevents reocclusion[1]. The decreasing intracellular amount and efflux of compound from the cells into the medium is measured. The measured CLint,efflux values are 0.13±0.06, 3.2±0.6, 10.1±2.3, and 110±2.8 for Digoxin, Fexofenadine, Napsagatran, and Rosuvastatin, respectively, thus representing drugs with a >800-fold range of efflux rates[2].
After the first hour of drug administration (from 0 to 60 min), the incorporated radioactivity into thrombi increased from baseline by 73±13, 67±22 and 32±10% in placebo, AP-1 and Napsagatran-treated rabbits, respectively. Statistical analysis confirm that thrombus growth in the placebo and AP-1 treated rabbits is not different. In contrast, reduction of 125I-fibrinogen incorporation by Napsagatran is statistical different from the placebo group (P<0.01)[3].
[1]. Pratico D, et al. Interaction of a thrombin inhibitor and a platelet GP IIb/IIIa antagonist in vivo: evidence thatthrombin mediates platelet aggregation and subsequent thromboxane A2 formation during coronary thrombolysis. J Pharmacol Exp Ther. 1997 Jun;281(3):1178-85. [2]. Lundquist P, et al. Prediction of in vivo rat biliary drug clearance from an in vitro hepatocyte efflux model. Drug Metab Dispos. 2014 Mar;42(3):459-68. [3]. Himber J, et al. Inhibition of tissue factor limits the growth of venous thrombus in the rabbit. J Thromb Haemost. 2003 May;1(5):889-95.
Kinase experiment: | Hepatocytes in 12-well plates are preloaded until a maximal intracellular concentration is reached. Measuring the compound efflux at maximal intracellular concentration gives the efflux at steady state. Preload times and compound concentrations are decided from measured uptake data in pilot experiments (Digoxin, 10 μM for 15 minutes; Fexofenadine, 1 μM for 30 minutes; Napsagatran, 10 μM for 30 minutes; and Rosuvastatin, 1 μM for 15 minutes). After preloading, the wells are washed three times in 37°C Krebs-Henseleit buffer with 10 mM HEPES (GIBCO) pH 7.4 (KHL) to ensure that the wells are free from remaining compound. Efflux experiments are started by adding 300 μL KHL (37°C) to each well. Cells are also lysed immediately after washing to determine the initial intracellular concentrations at the start of the experiment. The contribution of ABC-efflux transporter activity to the measured efflux is assayed using 0.5 μM of the inhibitors Elacridar and Fumitremorgin C (FTC)[2]. |
Animal experiment: | Rabbits[3]The experiment is initiated by a bolus injection followed by infusion of 125I-human fibrinogen. Increase of tracer uptake within 30 min infusion of more than 30% of background value is indicative of onset of thrombus growth and thus, the counts are set to zero and Rabbits receive either Napsagatran a specific thrombin inhibitor (10 µg/kg per min in continuous i.v. infusion) or repetitive i.v. bolus of the monoclonal antiRabbits TF antibody AP-1 (600 µg/kg) at hourly intervals. The placebo-treated Rabbits (control group) receive either saline infused at 1 mL/kg or four boli of an irrelevant IgG Rabbits mAb. |
References: [1]. Pratico D, et al. Interaction of a thrombin inhibitor and a platelet GP IIb/IIIa antagonist in vivo: evidence thatthrombin mediates platelet aggregation and subsequent thromboxane A2 formation during coronary thrombolysis. J Pharmacol Exp Ther. 1997 Jun;281(3):1178-85. | |
| Cas No. | 159668-20-9 | SDF | |
| 别名 | 奈沙加群,Ro 46-6240 hydrate; Ro 46-6240/010 hydrate | ||
| Canonical SMILES | O=C(NC[C@H]1CN(C(N)=N)CCC1)C[C@@H](C(N(C2CC2)CC(O)=O)=O)NS(C3=CC4=CC=CC=C4C=C3)(=O)=O.O | ||
| 分子式 | C26H36N6O7S | 分子量 | 576.67 |
| 溶解度 | Soluble in DMSO | 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 | 1.7341 mL | 8.6705 mL | 17.3409 mL |
| 5 mM | 0.3468 mL | 1.7341 mL | 3.4682 mL |
| 10 mM | 0.1734 mL | 0.867 mL | 1.7341 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet