The lipoxins are trihydroxy fatty acids containing a 7,9,11,13-conjugated tetraene. Lipoxin A4 (LXA4) was first described as a metabolite of 15-HpETE and/or 15-HETE when added in vitro to isolated human leukocytes. The material obtained in this manner consists of at least four distinct isomers: 5(S), 6(S); 5(S), 6(R); and the 11-trans and 11-cis isomers of each of these. 6(S)-LXA4 is one of the original four metabolites first identified by Serhan, Nicolaou, and Samuelsson. It was considered to be an artifact by these authors because it lacked the potency of the 5(S),6(R) isomer with respect to contraction of isolated guinea pig lung parenchymal strips. It has not been possible to isolate natural LXA4 from humans or other mammals in amounts sufficient for determination of absolute stereochemistry. Most authors refer to LXA4 as the 5(S)

Lipoxin A5 (LXA5) is produced by enzymatic transformation of EPA by leukocytes. LXA5 slowly contracts pulmonary parenchymal strips from guinea pig with similar potency to that of LXA4 and LXB4. However, LXA5 does not exert the vasodilatory effects on aortic smooth muscle exhibited by LXA4 and LXB4.

15(R)-HETE, a monohydroxy fatty acid, is synthesized from arachidonic acid via aspirin-acetylated COX-2, leading to the formation of specialized pro-resolving mediators 15(R)-lipoxin A4 and B4 through a transcellular mechanism involving 5-lipoxygenase (5-LO). Additionally, this compound is produced by the cytochrome P450 (CYP) isoform CYP2C9 and can be generated from arachidonic acid by COX-1 in human mast cells, where it accumulates due to its resistance to conversion into 15-KETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). As an agonist of PPARβ/δ, 15(R)-HETE induces the expression of a target gene in NIH3T3 cells, demonstrating its biological significance.