Phosphodiesterase 4 (PDE4) is a member of the PDE enzyme superfamily and inactivates cyclic adenosine monophosphate and cyclic guanosine monophosphate. PDE4 is the major PDE isoenzyme found in cells associated with inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). COPD is a preventable and treatable disease characterized by airflow obstruction that is not completely reversible. Here we introduce a highly selective and orally PDE4 inhibitor, Roflumilast.

Roflumilast has been approved by the FDA to improve lung function and reduce the frequency of COPD exacerbations.

Roflumilast inhibits PDE4 activity in human neutrophils with an IC50 of 0.8 nM. It has anti-inflammatory and immunomodulatory potential in various human leukocytes. It inhibits fMLP-induced LTB4 and reactive oxygen species (ROS) formation in neutrophils. Moreover, it inhibits fMLP- and C5a-induced ROS formation in eosinophils. And also, it inhibits lipopolysaccharide-induced tumor necrosis factor-α synthesis in dendritic cells. Then, it inhibits anti-CD3/anti-CD28 monoclonal antibody-stimulated proliferation in CD4+ T cells and reduces IL-2, IL-4, IL-5 and interference betaine-gamma release. Roflumilast can also be combined with long-acting β2-adrenoceptor agonists and short-acting muscarinic receptor antagonists to cover additional lung injuries.

pIgR-/- mice, which lack the polymeric immunoglobulin receptor for SIgA, spontaneously develop chronic obstructive pulmonary disease (COPD)-like pathology. Roflumilast (5 μg/g; p.o.; 3 months) prevents COPD-like lung inflammation and remodeling in pIgR-/- mice. It inhibits sustained activation of the innate immune response of the lung microbiota, thereby inhibiting progressive small airway remodeling and emphysema.

In summary, Roflumilast is an orally active PDE4 inhibitor that improves chronic obstructive pulmonary disease (COPD).


[1]. Rabe KF. Br J Pharmacol. 2011 May;163(1):53-67.

[2]. Hatzelmann A, et al. J Pharmacol Exp Ther. 2001 Apr;297(1):267-79.

[3]. Richmond BW, et al. Nat Commun. 2016 Apr 5;7:11240.