β2AR-IN-15

β2AR-IN-15 is a selective β2-adrenergic receptor (β2AR) antagonist with a K_d of 1.7 μM. β2AR-IN-15 binds to an intracellular β2AR region overlapping the G-protein binding site, enhancing orthosteric inverse agonist binding while negatively modulating binding of orthosteric agonists with EC₅₀ values of 1.9 and 0.48 μM. β2AR-IN-15 shows inhibitory effect on cAMP production and β-arrestin recruitment to activated β2AR. β2AR-IN-15 can be used for the research of cardiovascular and pulmonary diseases^[1]. In Vitro:β2AR-IN-15 (Compound 15) acts as a negative allosteric modulator for human β2AR reconstituted in nanodiscs, decreasing orthosteric agonist binding with an EC₅₀ of 1.9 μM and increasing inverse agonist binding with an EC₅₀ of 0.48 μM^[1].
β2AR-IN-15 binds directly to purified human β2AR with a K_d of 1.7 μM and a 1:1 binding stoichiometry^[1].
β2AR-IN-15 competes with the intracellular-binding nanobody Nb60 for binding to human β2AR, indicating its binding site is located on the receptor's intracellular region^[1].
β2AR-IN-15 inhibits transducer-promoted high-affinity agonist binding to human β2AR reconstituted in nanodiscs, with EC₅₀ values of 2.8 μM for Gαβγ and 2.2 μM for β-arrestin1, showing no bias between the two transducers^[1].
β2AR-IN-15 (1.25-50 μM; 20 min) inhibits isoproterenol-stimulated cAMP production in HEK-293 cells with endogenous β2AR and β-arrestin recruitment to chimeric β2V₂R, causing 7.1-fold and 7.4-fold right shifts of the isoproterenol EC₅₀, respectively^[1].
β2AR-IN-15 (1.25-50 μM; 20 min) selectively inhibits agonist-stimulated β-arrestin recruitment to human β2AR, with significantly reduced or no activity on β1AR, V₂R, VIPR, and AT₁R^[1].