Ensifentrine

Ensifentrine (RPL-554) is an inhaled dual inhibitor of PDE3 and PDE4 with IC₅₀s of 0.4 nM and 1479 nM, respectively. Ensifentrine blocks PDE3 and PDE4 enzymes, thereby increasing the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in lung cells, dilating the bronchi, and inhibiting the activation and migration of inflammatory cells. Ensifentrine can be used in the research of chronic obstructive pulmonary disease (COPD)^[1][2][3]. 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].