Resolution Pharmacology: Targeting the Annexin A1-FPR2/ALX Pathway

Annexin A1 (AnxA1) and its receptor formyl-peptide receptor type 2 (FPR2)-also termed lipoxin A₄ receptor (ALX) or FPR2/ALX-are highly effective modulators of several biological phenomena that enable the resolution of acute inflammation. These properties are reflected in non-redundant roles of this pro-resolving protein and its receptor in several preclinical models of disease. Here we reason on the translational opportunity posed by the fundamental science associated with AnxA1/FPR2 and propose potential clinical applications in disease areas where unablated inflammation and dysregulated immune cell activation and recruitment occur. We discuss AnxA1-derived compounds as well as the translational investigations based on FPR2 small-molecule agonists. In summary, we surmise that exploitation of the AnxA1/FPR2 pathway is a viable and amenable approach to establish resolution pharmacology as a new branch formed by innovative therapeutics that mimic endogenous processes of the resolution of inflammation.