GSK961081, also known as Batefenterol and TD-5959, is a Muscarinic Antagonist and β2-Agonist possessing both muscarinic antagonist (MA) and β2-adrenoceptor agonist (BA) properties (MABA). GSK-961081 displayed high affinity for hM2 (Ki = 1.4 nM), hM3 muscarinic receptors (Ki = 1.3 nM) and hβ2-adrenoceptors (Ki = 3.7 nM). GSK-961081 behaved 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.
|Cell lines||HEK or CHO-K1 cells|
|Preparation method||Cells were incubated with increasing concentrations of GSK-961081 for 20 minutes at 37°C. The cells were stimulated with an EC90 concentration of the muscarinic agonist oxotremorine. The EC90 concentration was determined by generating an agonist concentration-response curve with the same batch of cells before the experiment.|
|Concentrations||10, 30, and 100 nM|
|Incubation time||20 minutes|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10mM in DMSO|
Pharmacologic characterization of GSK-961081 (TD-5959), a first-in-class inhaled bifunctional bronchodilator possessing muscarinic receptor antagonist and β2-adrenoceptor agonist properties.
Hegde SS, et al. J Pharmacol Exp Ther. 2014 Oct;351(1):190-9. PMID: 25100753.
Dual-pharmacology muscarinic antagonist and β₂ agonist molecules for the treatment of chronic obstructive pulmonary disease.
Hughes AD, et al. Future Med Chem. 2011 Oct;3(13):1585-605. PMID: 21942250.
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