Batefenterol (GSK961081;TD-5959) is a novel muscarinic receptor antagonist and β₂-adrenoceptor agonist; displays high affinity for hM2, hM3 muscarinic and hβ₂-adrenoceptor with K_i values of 1.4, 1.3 and 3.7 nM, respectively.

Batefenterol is a novel first-in-class inhaled bifunctional compound possessing both muscarinic antagonist (MA) and β₂-adrenoceptor agonist (BA) properties (MABA). In competition radioligand binding studies at human recombinant receptors, batefenterol displays high affinity for hM2 (K_i=1.4 nM), hM3 muscarinic receptors (K_i=1.3 nM) and hβ₂-adrenoceptors (K_i=3.7 nM). Batefenterol behaves as a potent hβ₂-adrenoceptor agonist (EC₅₀=0.29 nM for stimulation of cAMP levels) with 440- and 320-fold functional selectivity over hβ₁- and hβ₃-adrenoceptors, respectively.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

In the guinea pig bronchoprotection assay, inhaled Batefenterol produces potent, dose-dependent inhibition of bronchoconstrictor responses via MA (ED₅₀=33.9 µg/mL), BA (ED₅₀=14.1 µg/mL), and MABA (ED₅₀=6.4 µg/mL) mechanisms. Significant bronchoprotective effects of Batefenterol are evident in guinea pigs via MA, BA, and MABA mechanisms for up to 7 days after dosing. In guinea pig isolated trachea expressing native muscarinic M3 and β₂, batefenterol produces smooth muscle relaxation through a dual mechanism involving competitive antagonism of the M3 receptor (EC₅₀=50 nM) and agonism of the β₂ receptor (EC₅₀=25 nM). The combined effect on both muscarinic receptors and β₂ receptors is more potent than either function working alone (EC₅₀=10 nM). Batefenterol exhibits a rapid rate of clearance and short half-life.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

In the guinea pig bronchoprotection assay, inhaled Batefenterol produces potent, dose-dependent inhibition of bronchoconstrictor responses via MA (ED₅₀=33.9 µg/mL), BA (ED₅₀=14.1 µg/mL), and MABA (ED₅₀=6.4 µg/mL) mechanisms. Significant bronchoprotective effects of Batefenterol are evident in guinea pigs via MA, BA, and MABA mechanisms for up to 7 days after dosing. In guinea pig isolated trachea expressing native muscarinic M3 and β₂, batefenterol produces smooth muscle relaxation through a dual mechanism involving competitive antagonism of the M3 receptor (EC₅₀=50 nM) and agonism of the β₂ receptor (EC₅₀=25 nM). The combined effect on both muscarinic receptors and β₂ receptors is more potent than either function working alone (EC₅₀=10 nM). Batefenterol exhibits a rapid rate of clearance and short half-life.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Hegde SS, et al. Pharmacologic characterization of GSK-961081 (TD-5959), a first-in-class inhaled bifunctional bronchodilator possessing muscarinic receptor antagonist and β2-adrenoceptor agonist properties. J Pharmacol Exp Ther. 2014 Oct;351(1):190-9.  [Content Brief]

  . Hughes AD, et al. Discovery of (R)-1-(3-((2-chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, batefenterol): first-in-class dual pharmacology multivalent muscarinic antagonist and β? agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD). J Med Chem. 2015 Mar 26;58(6):2609-22.  [Content Brief]