BIBR 953

• 产品号: S2196
• CAS号: 211914-51-1
• 分子式: C25H25N7O3
• 分子量: 471.5111
• 保 存: -20°C

产品别名

• 标题: BIBR 953
• IUPAC标准名: 3-[1-(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-1,3-benzodiazol-5-yl)-N-(pyridin-2-yl)formamido]propanoic acid
• IUPAC传统名: dabigatran
• 别名: BIBR953; Dabigatran; Pradaxa

产品登记号

• CAS号: 211914-51-1

产品性质

• 作用靶点: thrombin
• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: BIBR 953 (Dabigatran, Pradaxa) is potent nonpeptide thrombin inhibitor with an IC50 of 9.3 nM.
• Targets: Thrombin
• IC50: 9.3 nM ^[1]
• In Vitro: BIBR 953 is a very potent anticoagulant. BIBR 953 shows that the terminal phenyl can be substituted by the more hydrophilic 2-pyridyl group without substantial loss of activity. BIBR 953 inhibits thrombin, plasmin, factor Xa, trypsin, tPA and activated protein C with Ki of 4.5 nM, 1.7 μM, 3.8 μM, 50 nM, 45 μM and 20 μM, respectively. ^[1] BIBR 953 specifically and reversibly inhibits thrombin. ^[2]
• In Vivo: BIBR 953 exhibits the most favorable activity profile following i.v. administration to rats. ^[1] The bioavailability of dabigatran after p.o. administration of dabigatran etexilate is 7.2%. Dabigatran is predominantly excreted in the feces after p.o. treatment and in the urine after i.v. treatment. The mean terminal half-life of dabigatran is approximately 8 hours. Dabigatran acylglucuronides accounts for 0.4% and 4% of the dose in urine after p.o. and i.v. dosing, respectively. ^[3]
• Clinical Trials: Dabigatran has entered in a phase III clinical trial in the treatment of atrial fibrillation.
• Features: Dabigatran is a reversible, competitive, direct thrombin inhibitor.

Protocol

• Protocol: Kinase Assay ^[1]
• Measurement of thrombin inhibition: The thrombin inhibitory effects (IC50) of BIBR 953 is determined with a commercially available chromogenic assay. Human thrombin (0.042 U/mL) is preincubated for 10 minutes at 37 °C with 10 different dilutions (concentration range of 0.003 μM -100 μM) of BIBR 953 dissolved in DMSO or with DMSO as control. Upon addition of the preincubation mixture to the chromogenic substrate, tosyl-glycyl-prolyl-arginine-4-nitranilide acetate, nitraniline is cleaved by thrombin and the increase in absorbance at 405 nm, related to the free nitraniline, is measured in a spectrophotometer. By plotting the absorbance at 405 nm vs the concentration of BIBR 953, the concentration that induces a 50% thrombin inhibition (IC50) is calculated. All measurements are performed in duplicate, and the mean values of both determinations are represented.
• Protocol: Animal Study ^[1]
• Animal Models: Rats
• Administration: Administered via i.v.

References

• References: [1] Hauel NH, et al. J Med Chem. 2002, 45(9), 1757-1766.
• References: [2] Stangier J, et al. Br J Clin Pharmacol. 2007, 64(3), 292-303.
• References: [3] Blech S, et al. Drug Metab Dispos. 2008, 36(2), 386-399.

参考文献

• Hauel NH, et al. J Med Chem. 2002, 45(9), 1757-1766.
• Stangier J, et al. Br J Clin Pharmacol. 2007, 64(3), 292-303.
• Blech S, et al. Drug Metab Dispos. 2008, 36(2), 386-399.