TD-5471 hydrochloride is a selective and potent long-acting human β2-adrenergic receptor agonist for the treatment of chronic obstructive pulmonary disease (COPD).

In an in vitro guinea pig trachea model, TD-5471 exhibits potent activity with a slow onset. Its potency is evident, as indicated by a pEC50 of 8.7 in the guinea pig tracheal ring assay. Notably, TD-5471 is structurally distinct from Milveterol, and its prolonged duration of action aligns with a correlation observed in other long-acting β2-agonist discovery programs, specifically related to hydrophobicity[1].

In an in vivo guinea pig model of bronchoprotection, TD-5471 demonstrates a prolonged and dose-dependent duration of action. The efficacy of TD-5471 is notably high, as evidenced by its excellent potency measured 1.5 hours after nebulized dosing. To ensure suitability for once-daily dosing in humans, a 72-hour time point is chosen, considering that a high dose of Salmeterol (300 μg/mL) provides bronchoprotection lasting ≥24 hours in this model.
At the 72-hour time point, TD-5471-mediated bronchoprotection remains dose-dependent and significantly surpasses the efficacy of Salmeterol at nebulizer concentrations of ≥30 μg/mL[1].