Vilanterol-GW642444X-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVilanterolCat. No.: HY-14300CAS No.: 503068-34-6Synonyms: GW642444X; GW642444分式: CHClNO分量: 486.43作靶点: Adrenergic Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Pure form -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1

2、month溶解性数据体外实验 DMSO : 100 mg/mL (205.58 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0558 mL 10.2790 mL 20.5579 mL5 mM 0.4112 mL 2.0558 mL 4.1116 mL10 mM 0.2056 mL 1.0279 mL 2.0558 mL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，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的

3、溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (6.17 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3 mg/mL (6.17 mM); Clear solution

4、1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 3 mg/mL (6.17 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Vilanterol (GW642444; GW 642444X)吸型长效2激动剂。IC50 & Target pEC50: 10.370.05 (2-adrenoceptor), 6.980.03 (1-adrenoceptor), 7.360.03 (3-adrenoceptor) 1体外研

5、究 The selectivity of Vilanterol for 2-AR over the other -AR receptor subtypes (2 and 3) is established bytesting the ability of Vilanterol to elicit concentration-dependent increases in cAMP in CHO cells expressinghuman 1-, 2-, and 3-AR. Vilanterol is demonstrated to be highly selective for the 2-AR

6、 with at least a1000-fold selectivity over both 2- and 3-AR subtypes. This analysis results in a low-affinity pKD for3HVilanterol of 9.440.07 (n=4) in the presence Gpp(NH)p and a high-affinity pKD of 10.820.12 (n=4) anda low-affinity pKD 9.470.17 (n=4) in the absence of Gpp(NH)p. In addition, a low-

7、affinity pKD for3HVilanterol of 9.520.24 (n=4) in the absence of Gpp(NH)p (37C) is observed 1. Vilanterol trifenatate isa novel inhaled long-acting 2-agonist with inherent 24 h activity in vitro in development as a combinationwith the inhaled corticosteroid fluticasone furoate for both COPD and asth

8、ma 2. Vilanterol is a novel long-acting 2-agonist (LABA) with inherent 24-hour activity for once-daily clinical treatment of chronic obstructivepulmonary disease (COPD) and asthma in combination with the inhaled novel corticosteroid fluticasonefuroate, also active for 24 hours 3.PROTOCOLKinase Assay

9、 1 Saturation, association, and dissociation binding studies are performed for 3HVilanterol to determinereceptor binding kinetics at the 2-AR (equilibrium dissociation constant (KD), total number of receptors(Bmax), association rate (kon), and dissociation rate (koff) are calculated). For saturation

10、 binding,membranes (in a volume of 1.4 mL to avoid ligand depletion) are incubated with increasing concentrations of3HVilanterol (0.01-1.3 nM) for 5 h before filtration. For association binding, membranes are incubated withdifferent concentrations of 3HVilanterol (0.1-1.9 nM) for varying incubation

11、times up to 1 h before filtration.For dissociation binding, membranes are preincubated for 1 h with a fixed concentration of 3HVilanterol(1.1 nM) before dissociation is initiated by a 1:20 dilution in binding buffer (containing 10 M cold Vilanterol)and then incubated for varying times up to 8 h befo

12、re filtration. Saturation binding is also completed for3HCGP12177 (increasing concentrations of 0.01-2.8 nM) in the same format as described above for3HVilanterol. To determine the affinity of 2-AR agonists and antagonists, competition binding displacementstudies are completed in which membranes are

13、 incubated with a fixed concentration of 3HVilanterol (0.2nM) and increasing concentrations of unlabeled agonist/antagonist for 5 h before filtration. All competitionbinding displacement studies are completed in the presence of 100 M Gpp(NH)p to ensure that bindingcurves are monophasic 1.MCE has not

14、 independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Eur J Pharmacol. 2017 Oct 5;812:147-154. J Neuroimmunol. 2019 Mar 28;332:37-48. Mental Health and Neuroscience Institute. University of Alberta. 2016 Sep.

15、Centre for Neuroscience. University of Alberta. 2016.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Slack RJ, et al. In vitro pharmacological characterization of vilanterol, a novel long-acting 2-adrenoceptor agonist with 24-hour durationof action. J Pharmacol Exp Ther. 2013 J

16、an;344(1):218-302. Kempsford R, et al. Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjectsand demonstrates prolonged bronchodilation in subjects with asthma and COPD. Pulm Pharmacol Ther. 2013 Apr;26(2):256-3. Harrell AW, et al. Metabolism and disposition of Vilanterol, a long-acting (2)-adrenoceptor agonist for inhalation use in humans. DrugMetab Dispos. 2013 Jan;41(1):89-100.4. Calzetta L, et al. Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi. E