olodaterol hydrochloride

Olodaterol (BI1744) hydrochloride is a selective, long acting β2-adrenoceptor (β2-AR) agonist (EC50=0.1 nM and pKi= 9.14 for human β2-adrenoceptor, respectively). Olodaterol can be used for chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis[1][2][3].

Research Areas >> Endocrinology

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Inflammation/Immunology

β2 adrenoceptor:0.1 nM (EC50)

Olodaterol hydrochloride (0.1~10 nM; fibroblasts) interferes with FGF-induced phosphorylation of signalling cascades[2]. Olodaterol hydrochloride (0.001~10 nM; fibroblasts) attenuates growth factor-induced motility and proliferation[2]. Olodaterol hydrochloride (0.001~1000 nM; 0.5 hours; fibroblasts) increases intracellular cAMP in a concentration-dependent manner. Olodaterol hydrochloride (0~10 nM; 0.5 hours; fibroblasts) concentration-dependently inhibits the PICP increase with maximal efficacy of 70 % at 10 nM. Olodaterol hydrochloride has a subnanomolar affinity for the β2-AR (pKi=9.14) and is selective for this receptorin comparison with the β1-AR and β3-AR subtypes[2]. Western Blot Analysis[2] Cell Line: Fibroblasts Concentration: 0.1~10 nM Incubation Time: Result: Interfered with FGF-induced phosphorylation of signalling cascades. Cell Proliferation Assay[2] Cell Line: Fibroblasts Concentration: 0.001~10 nM Incubation Time: Result: Attenuated growth factor-induced motility and proliferation.

Olodaterol (1 mg/kg; inhal.; 21 days) accelerats body weights recovery back to control levels (at day 21) and attenuats TGF-β-induced lung fibrosis[2]. Olodaterol (0.1~3 μg/kg; inhal.; 5 hours) induces a dose-dependent bronchoprotection[3]. Olodaterol (0.3 and 0.6 μg/kg; inhal.; 24 hours) induces a maximal bronchoprotection of approximately 60 % after 0.5 hours[3]. Animal Model: Lung fibrosis C57BL/6 mice Dosage: 1 mg/mL Administration: Inhal.; 21 days Result: Accelerated body weight recovery back to control levels (at day 21) and attenuated TGF-β-induced lung fibrosis. Animal Model: Guinea Pigs Dosage: 0.1~3 μg/kg Administration: Inhal.; 5 hours Result: Induced a dose-dependent bronchoprotection. Animal Model: Dogs Dosage: 0.3 and 0.6 μg/kg Administration: Inhal.; 24 hours Result: Olodaterol (0.6 μg/kg) induced a maximal bronchoprotection of approximately 60 % after 0.5 h.

[1]. Xing G, et al. Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists. Bioorg Med Chem. 2020;28(1):115178.

[2]. Herrmann FE, et al. Olodaterol shows anti-fibrotic efficacy in in vitro and in vivo models of pulmonary fibrosis. Br J Pharmacol. 2017;174(21):3848-3864.

[3]. Bouyssou T, et al. Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models [published correction appears in J Pharmacol Exp Ther. 2013 Jul;346(1):161]. J Pharmacol Exp Ther. 2010;334(1):53-62.