Ensifentrine CAS# 1884461-72-6

Ensifentrine (RPL554) is a dual phosphodiesterase (PDE)3 and PDE4 inhibitor with both bronchodilatory and anti-inflammatory activities. In vitro, Ensifentrine inhibited PDE3A and PDE4B with IC₅₀ values of 0.26 nM and 510 nM, respectively, elevating intracellular cAMP levels and inducing relaxation of isolated human bronchial smooth muscle. It also suppressed TNF-α and IL-8 release from human monocytes (IC₅₀ ≈ 100 nM). In vivo, in anesthetized guinea pigs, inhaled Ensifentrine (0.03–1 mg/kg) produced dose-dependent bronchodilation comparable to salbutamol and reduced airway hyperresponsiveness to histamine. In ovalbumin-sensitized guinea pigs and mice, repeated dosing (0.1–1 mg/kg) reduced eosinophilic infiltration and inflammatory cytokine levels in bronchoalveolar lavage fluid. These results demonstrate potent dual PDE3/4 inhibition leading to both bronchodilation and anti-inflammatory effects in preclinical respiratory models.