BIBR 953 (Dabigatran, Pradaxa)
(Synonyms: 达比加群; BIBR 953; BIBR 953ZW) 目录号 : GC16293
A thrombin inhibitor
Cas No.:211914-51-1
Sample solution is provided at 25 µL, 10mM.
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BIBR 953 is a potent, reversible, and direct inhibitor of thrombin with IC50 value of 9.3nM [1].
BIBR 953 shows a favorable selectivity profile and strong activity in vitro with a Ki value of 4.5nM. It also exhibits the best activity profile in vivo following administration to rats. BIBR 953 is designed to be converted into an orally active prodrug BIBR 1048 due to its highly polar, zwitterionic nature and poor oral absorption. BIBR 953 inhibits thrombin in a competitive fashion. This inhibition is rapid and reversible. BIBR 953 inhibits both clot-bound and free thrombin. BIBR 953 is demonstrated to have an anticoagulant efficacy both in vitro and ex vivo. Since thrombin can affect cell behavior and response in various tissue types via PAR signaling, BIBR 953 is found to be beneficial in many diseases including inflammation, infection, fibrosis and cancer. Clinical trials show that BIBR 953 is a highly effective anticoagulant with a good safety profile [1, 2].
References:
[1] Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem. 2002 Apr 25;45(9):1757-66.
[2] van Ryn J, Goss A, Hauel N, Wienen W, Priepke H, Nar H, Clemens A. The discovery of dabigatran etexilate. Front Pharmacol. 2013 Feb 12;4:12.
| Thrombin inhibition assay [1]: | |
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Chromogenic assay |
Human thrombin (0.042 U/mL) was pre-incubated for 10 mins at 37 °C with 10 different dilutions (concentration range of 0.003 ~ 100 μM) of BIBR 953 dissolved in DMSO or with DMSO as control. Upon addition of the pre-incubation mixture to the chromogenic substrate, tosyl-glycyl-prolyl-arginine-4-nitranilide acetate, nitraniline was cleaved by thrombin and the increase in absorbance at 405 nm, related to the free nitraniline, was measured in a spectrophotometer. By plotting the absorbance at 405 nm vs the concentration of the test compound, IC50 was calculated. |
| In intro experiment [2]: | |
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Samples |
Adult and neonatal platelet-poor plasma |
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Preparation method |
The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0, 40, 110, 180, 250 or 320 ng/mL |
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Applications |
Without the presence of BIBR 953, neonatal and adult samples showed similar results on the time to clot initiation. In neonatal samples, BIBR 953 significantly delay clotting in a dose-dependent manner, with the difference increasing from 3 times for 40 ng/mL BIBR 953 to 9 times for 320 ng/mL BIBR 953. |
| Animal experiment [1]: | |
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Animal models |
Rats |
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Dosage form |
i.v. |
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Applications |
Compared with all of the inhibitors tested, BIBR 953 exhibited the strongest activity and the longest duration of action. Besides, it was well-tolerated in rats up to the highest dose of 10 mg/kg. However, BIBR 953 was not orally active because it was a very polar, a permanently charged molecule with a logP of -2.4 (n-octanol/buffer, pH 7.4). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem. 2002 Apr 25;45(9):1757-66. [2]. Nossair FF, Chan HHW, Gantioqui J, Atkinson HM, Berry LR, Chan AKC. In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure. Blood Coagul Fibrinolysis. 2017 May 12. |
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| Cas No. | 211914-51-1 | SDF | |
| 别名 | 达比加群; BIBR 953; BIBR 953ZW | ||
| 化学名 | 3-[[2-[(4-carbamimidoylanilino)methyl]-1-methylbenzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoic acid | ||
| Canonical SMILES | CN1C2=C(C=C(C=C2)C(=O)N(CCC(=O)O)C3=CC=CC=N3)N=C1CNC4=CC=C(C=C4)C(=N)N | ||
| 分子式 | C25H25N7O3 | 分子量 | 471.5 |
| 溶解度 | 12.5 mg/mL in 0.1 M HCL (Need ultrasonic); < 0.1 mg/mL in Water; < 1 mg/mL 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1209 mL | 10.6045 mL | 21.2089 mL |
| 5 mM | 0.4242 mL | 2.1209 mL | 4.2418 mL |
| 10 mM | 0.2121 mL | 1.0604 mL | 2.1209 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
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet