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Umeclidinium bromide

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Chemical Structure| 869113-09-7 同义名 : 溴化乌梅丁铵 ;GSK573719A;Umeclidinium (bromide);GSK-573719, GSK573719, GSK 573719, GSK-573719A, GSK573719A, GSK 573719A, Incruse Ellipta, Umeclidinium bromide;GSK573719
CAS号 : 869113-09-7
货号 : A535937
分子式 : C29H34BrNO2
纯度 : 95%
分子量 : 508.49
MDL号 : -
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(49.17 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • mAChR
描述 Activation of muscarinic subtype 3 (M3) muscarinic cholinergic receptors (mAChRs), which is highly expressed on the airway smooth muscle, increases airway tone, whereas its blockade improves lung function and quality of life in patients with pulmonary diseases. Umeclidinium Bromide is a novel mAChR antagonist with the affinity (Ki) for the cloned human M1-M5 mAChRs ranged from 0.05 to 0.16 nM. In cells containing the human recombinant M3 mAChR, the CRC (concentration-response curves) obtained with Ach was shifted rightward in the presence of Umeclidinium Bromide (1–1000 nM) in a concentration-dependent manner. Additional cellular studies showed that the effects of Umeclidinium Bromide on the M3 mAChR–mediated activity were slowly reversible. Pretreatment of CHO cells with Umeclidinium Bromide (3.3–330 nM for 30 minutes) produced rightward displacement of the Ach CRC comparable to that obtained previously. The changes in contractile activity were concentration-dependently blocked by preincubation (120 minutes) of the tissues with Umeclidinium Bromide (1–100 nM), thereby displacing the Cch-CRC to the right in a parallel manner. The time to 50% of maximal relaxation(termed ON t1/2) for Umeclidinium Bromide was concentration-dependent and decreased in value as the concentration of antagonist was increased. When administered intranasally as a solution, Umeclidinium Bromide blocked nebulized methacholine (30 mg/ml or ED80 value for maximal bronchoconstriction) in a dose-dependent manner (ED50 = 0.02 μg per mouse measured 5 hours after instillation). Intratracheal instillation of Umeclidinium Bromide (0.25, 2.5, and 25 μg per guinea pig) dose dependently blocked the increase in Penh elicited by aerosolized Ach. At the highest dose of Ach (100 μg i.v.), significant inhibition, i.e., 74.4%, P＜0.05, was obtained 4 hours after instillation of 0.25 μg per guinea pig of Umeclidinium Bromide[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.97mL

0.39mL

0.20mL

9.83mL

1.97mL

0.98mL

19.67mL

3.93mL

1.97mL
参考文献

[1]Salmon M, Luttmann MA, et al. Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptorsfor treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.

[2]Cazzola M, Page CP, et al. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012 Jul;64(3):450-504.

[3]Salmon M, Luttmann MA, Foley JJ, et al. Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013;345(2):260‐270