PF-610355 hydrochloride is a β2 - adrenergic receptor ( β2-AR ) full agonist with selectivity for β1-adrenergic receptors. PF-610355 hydrochloride increases intracellular cAMP levels, induces sustained tracheal smooth muscle relaxation, and inhibits acetylcholine-induced bronchoconstriction. PF-610355 hydrochloride can be used in research related to chronic obstructive pulmonary disease, asthma, and respiratory system diseases [1] [2] [3].
In Vivo, PF-610355 (0.1-1 μg; intratracheal; single dose) hydrochloride exhibits an intratracheal ED50 of 0.1 μg for inhibiting acetylcholine-induced bronchoconstriction in anesthetized Beagle dogs, with a duration of action exceeding 8 hours at both ED50 and 10× ED50 doses and a therapeutic index of at least 10[2].
In Vitro, PF-610355 hydrochloride exhibits full agonist activity at human β2-adrenergic receptors in CHO cells with an EC50 of 0.26 nM, and has a β1/β2 selectivity ratio of 220[2]. The intrinsic clearance of PF-610355 hydrochloride in human liver microsomes is 54 μL/min/mg. Approximately 80% of phase I metabolism is mediated by CYP3A4, while glucuronidation also occurs, with a corresponding Clint of 33 μL/min/mg[2].
References:
[1]. Fuso L, et al. Long-acting beta-agonists and their association with inhaled corticosteroids in COPD. Curr Med Chem. 2013;20(12):1477-1495.
[2]. Glossop PA, et al. Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. J Med Chem. 2010;53(18):6640-6652.
[3]. Timalsina D, et al. Pharmacologic Activities of Plant-Derived Natural Products on Respiratory Diseases and Inflammations. Biomed Res Int. 2021;2021:1636816. Published 2021 Oct 4.
In Vivo, PF-610355 (0.1-1 μg; intratracheal; single dose) hydrochloride exhibits an intratracheal ED50 of 0.1 μg for inhibiting acetylcholine-induced bronchoconstriction in anesthetized Beagle dogs, with a duration of action exceeding 8 hours at both ED50 and 10× ED50 doses and a therapeutic index of at least 10[2].
In Vitro, PF-610355 hydrochloride exhibits full agonist activity at human β2-adrenergic receptors in CHO cells with an EC50 of 0.26 nM, and has a β1/β2 selectivity ratio of 220[2]. The intrinsic clearance of PF-610355 hydrochloride in human liver microsomes is 54 μL/min/mg. Approximately 80% of phase I metabolism is mediated by CYP3A4, while glucuronidation also occurs, with a corresponding Clint of 33 μL/min/mg[2].
References:
[1]. Fuso L, et al. Long-acting beta-agonists and their association with inhaled corticosteroids in COPD. Curr Med Chem. 2013;20(12):1477-1495.
[2]. Glossop PA, et al. Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. J Med Chem. 2010;53(18):6640-6652.
[3]. Timalsina D, et al. Pharmacologic Activities of Plant-Derived Natural Products on Respiratory Diseases and Inflammations. Biomed Res Int. 2021;2021:1636816. Published 2021 Oct 4.