Drugs That Target the FPR2 Receptor


The seven-transmembrane G protein-coupled receptor family fpr2 (FPR2) is the most promiscuous member of this group and responds to a wide variety of endogenous or exogenous ligands, ranging from peptides to lipids. The ligands bound to FPR2 can induce either proinflammatory or anti-inflammatory responses depending on the type of binding site and signaling pathway, e.g. the bacterial antimicrobial peptide LL-37 binds to FPR2 to trigger neutrophil migration, while LXA4, RvD1, and annexin A1 bind to a different part of the FPR2 extracellular domain to activate anti-inflammatory responses.

These dual responses are related to the lipid composition of the bound ligand. Lipid agonists bind to the FPR2 extracellular loop and the 7TM region, while peptide and protein ligands bind to the NH2-terminal domain and the 1st two extracellular loops.

The ligands binding to FPR2 can modulate the cell’s metabolism and induce anti-inflammatory effects in nonimmune cells. They can also prevent fibrosis and inhibit tumor progression in hepatocellular carcinoma.

FPR2 agonists have been shown to suppress the inflammatory response in human liver cancer cells and in mouse models of hepatocellular carcinoma. In addition, these compounds have been shown to increase apoptosis in tumor cells and reduce hepatocellular carcinoma cell proliferation. In this article, Youngmi Jung and Chanbin Lee from Pusan National University in Korea discuss how drugs that target the fpr2 receptor could be used to protect against hepatocellular carcinoma and other liver diseases.


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