Vilanterol

Vilanterol is a novel and selective agonist of β2-AR with a PEC50 value of 10.37±0.05 [1].

Vilanterol is a novel long-acting β2-AR agonist (LABA) with 24h activity in development for inhaled once daily treatment. In the radioligand binding studies, Vilanterol has shown the binding affinity in the one-affinity site model with pKD values of 9.44±0.07 and 10.82±0.12 in the presence Gpp(NH)p and absence Gpp(NH)p, respectively. In dissociation studies, Vilanterol has been reported to bind from the β2-AR with a dissociation t1/2 value of 3.5 min in the presence of Gpp(NH)p. Vilanterol has been found to have a good selectivity for β2-AR over the other β-AR receptor subtypes(β1and β3) with pEC50 values of 10.37±0.05, 6.98±0.03 and 7.36±0.03, respectively. Vilanterol has exhibited at least 1000-fold selectivity over both β1-and β3-AR subtypes [1].

References:
[1] Slack RJ1, Barrett VJ, Morrison VS, Sturton RG, Emmons AJ, Ford AJ, Knowles RG.In vitro pharmacological characterization of vilanterol, a novel long-acting β2-adrenoceptor agonist with 24-hour duration of action.J Pharmacol Exp Ther. 2013 Jan; 344(1):218-30.

A randomised, phase III trial of once-daily fluticasone furoate/vilanterol 100/25 mug versus once-daily vilanterol 25 mug to evaluate the contribution on lung function of fluticasone furoate in the combination in patients with COPD.[Pubmed:28137501]

Respir Med. 2017 Feb;123:8-17.

BACKGROUND: The contribution of fluticasone furoate (FF) on lung function in the FF/Vilanterol (VI) 100/25 mug combination has been demonstrated numerically, but not statistically. METHODS: This multicentre, randomised, double-blind, controlled trial (GlaxoSmithKline study number 200820; clinicaltrials.gov NCT02105974) enrolled >/=40-year-old patients with chronic obstructive pulmonary disease (COPD), a >/=10-pack-year smoking history, a post-bronchodilator forced expiratory volume in 1 s (FEV1) 30-70% of the predicted value, a FEV1/forced vital capacity ratio of /=1 COPD exacerbation in the previous 12 months requiring corticosteroids, antibiotics and/or hospitalisation, and current COPD symptoms. Participants received FF/VI 100/25 mug or VI 25 mug once daily. The primary endpoint was the change from baseline in trough FEV1 at day 84. FINDINGS: 1620 patients were randomised and received at least one dose of FF/VI 100/25 mug (n = 806) or VI 25 mug (n = 814). At day 84, the FF/VI 100/25 mug group showed an adjusted mean treatment difference of 34 mL over VI 25 mug in change from baseline trough FEV1 (95% confidence interval [CI] 14-55; p = 0.001). There was no significant difference between the groups in the percentage of rescue medication-free 24-h periods. The FF/VI 100/25 mug group demonstrated a 42% risk reduction compared with the VI 25 mug group in time to first moderate/severe COPD exacerbation (95% CI 22-57; nominal p < 0.001). The incidence of on-treatment adverse events was similar between the groups. INTERPRETATION: The contribution of FF in the FF/VI 100/25 mug combination on lung function in COPD was statistically significant. FUNDING: GlaxoSmithKline.

Umeclidinium/vilanterol as step-up therapy from tiotropium in patients with moderate COPD: a randomized, parallel-group, 12-week study.[Pubmed:28280319]

Int J Chron Obstruct Pulmon Dis. 2017 Feb 24;12:745-755.

INTRODUCTION: Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/Vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO). METHODS: In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for >/=3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score >/=1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 microg or TIO 18 microg for 12 weeks. Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs). RESULTS: Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: -0.1 puffs/d [95% CI: -0.2-0.0]; P/=1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P

A randomized trial of once-daily fluticasone furoate/vilanterol or vilanterol versus placebo to determine effects on arterial stiffness in COPD.[Pubmed:28176907]

Int J Chron Obstruct Pulmon Dis. 2017 Jan 19;12:351-365.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD. MATERIALS AND METHODS: The effects of once-daily inhaled fluticasone furoate/Vilanterol (FF/VI) 100/25 microg, VI 25 microg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV >/=11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial. Eligible patients were >/=40 years old, with >/=10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity

Vilanterol (GW642444) is a long-acting β2-adrenoceptor (β2-AR) agonist with 24 h activity. The pEC50s for β2-AR,β1-AR and β3-AR is 10.37±0.05, 6.98±0.03 and 7.36±0.03, respectively.

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