Ensifentrine

Ensifentrine (RPL-554) is an inhaled first-in-class dual inhibitor of phosphodiesterase 3 (PDE3) and PDE4 with IC₅₀s of 0.4 nM and 1479 nM, respectively. Ensifentrine has bronchoprotective and anti-inflammatory activities. Ensifentrine can be used for chronic obstructive pulmonary disease (COPD) research^[1][2]. In Vitro:Ensifentrine (RPL-554) inhibits, in a concentration-dependent manner, lipopolysaccharide-induced TNF-α release from human monocytes (IC₅₀ of 0.52 μM) and proliferation of human mononuclear cells to phytohemagglutinin (IC₅₀ of 0.46 μM)^[1].
Electrical field stimulation-induced contraction of guinea pig superfused isolated tracheal preparations is significantly inhibited by Ensifentrine (10 μM). Contractile responses are suppressed for up to 12 h after termination of superfusion with RPL-554 demonstrating a long duration of action^[1]. In Vivo:Ensifentrine (RPL-554; 10 mg/kg; Oral administration; once) significantly inhibits eosinophil recruitment following antigen challenge in ovalbumin-sensitized guinea pigs^[1].
The inhalation of dry powder containing Ensifentrine by conscious guinea pigs (25% in micronized lactose) 1.5 h before antigen exposure significantly inhibits the recruitment of eosinophils to the airways^[1].
Exposure of conscious guinea pigs to inhalation of dry powder containing Ensifentrine (2.5%) in micronized lactose significantly inhibits histamine-induced plasma protein extravasation in the trachea and histamine-induced bronchoconstriction over a 5.5-h period^[1].