Therapeutic anti-inflammatory potential of formyl-peptide receptor agonists.
The need for novel anti-inflammatory drugs justifies the search for innovative targets that could satisfy this goal. For quite some time now, we have proposed the study of endogenous anti-inflammation as a distinctive approach to the discovery of new drugs. This approach requires development of new compounds that activate specific receptor targets to downregulate the cellular and tissue pathways operative in the host during inflammation. Here we dwell on a family of G-protein coupled receptors (GPCR) termed FPRs, acronym for formyl-peptide receptors. With three and seven members in man and mouse, respectively, these receptors harness many biological functions, spanning odour perception and hair growth, to the control of multiple facets (pain; cell migration; oxidative burst; xenobiotic engulfment) of the inflammatory reaction. We focus on FPR biology with particular attention to molecules able to produce pharmacological effects by interacting with these GPCRs, describing endogenous agonists of FPRs and, more relevantly, the current development of synthetic agonists. Besides being potential leads for the development of the anti-inflammatory therapeutics of the future, these compounds could also help clarify the properties and roles that each FPR might play in the complex network of pathways that is inflammation. We conclude that FPR2 agonists could be valid warhorses for defining a novel philosophy for anti-inflammatory drug discovery programmes: mimicking - with new compounds - the way our body disposes of inflammation could be a viable approach to regulate aberrant inflammatory responses as in the case of several chronic rheumatic and cardiovascular pathologies.
Dufton
Neil
N
The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
Perretti
Mauro
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D044042:Receptors, Formyl Peptide / Q000819:agonists*; D044067:Receptors, Lipoxin / Q000819:agonists
D000893:Anti-Inflammatory Agents; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin