BATEFENTEROL

GSK-961081 was tested in binding assays against 83 cellular targets including receptors, transporters, channels, and enzymes at a single saturating concentration of 1 μM (>700-fold above the M3 receptor Ki value). At the vast majority of the targets, GSK-961081 produced <80% inhibition of specific binding. GSK-961081 had moderate to low affinity at the human D3 (Ki = 61 nM), human H1 (Ki = 98 nM), and human I2 (Ki = 320 nM) receptors and weak agonist activity at the human 5-HT4C (IA 18% of 5-HT [serotonin]). These off-target activities were considered biologically insignificant given the significantly greater potency at the three principal on-targets (M2, M3, and β2).

GSK-961081 displayed approximately 120- and 300-fold selectivity for hβ2- over hβ1- and hβ3-adrenoceptors, respectively, in the radioligand assay. GSK-961081 was greater than 400- and 300-fold selective for hβ2- over hβ1- and hβ3-adrenoceptors, respectively in EMR evaluation.