Advances in the Chemistry and Biology of Specialised Pro-Resolving Mediators (SPMs).

This review article assembles key recent advances in the synthetic chemistry and biology of specialised pro-resolving mediators (SPMs). The major medicinal chemistry developments in the design, synthesis and biological evaluation of synthetic SPM analogues of lipoxins and resolvins have been discussed. These include variations in the top and bottom chains, as well as changes to the triene core, of lipoxins, all changes intended to enhance the metabolic stability whilst retaining or improving biological activity. Similar chemical modifications of resolvins are also discussed. The biological evaluation of these synthetic SPMs is also described in some detail. Original investigations into the biological activity of endogenous SPMs led to the pairing of these ligands with the FPR2/LX receptor, and these results have been challenged in more recent work, leading to conflicting results and views, which are again discussed.