The lipoxygenases (LOXs) are a structurally related family of non-heme iron dioxygenases that function in the production, and in some cases metabolism, of fatty acid hydroperoxides. For arachidonic acid as substrate, these products are hydroperoxyeicosatetraenoic acids (HPETEs). In humans there are five lipoxygenases, the 5S-(arachidonate : oxygen 5-oxidoreductase), 12R-(arachidonate 12-lipoxygenase, 12R-type), 12S-(arachidonate : oxygen 12-oxidoreductase), and two distinct 15S-(arachidonate : oxygen 15-oxidoreductase) LOXs that oxygenate arachidonic acid in different positions along the carbon chain and form the corresponding 5S-, 12S-, 12R-, or 15S-hydroperoxides, respectively.

An 8-LOX (EC 1.13.11.40, arachidonate:oxygen 8-oxidoreductase) may be the mouse orthologue of 15-LOX-2 [5]. Some general LOX inhibitors are nordihydroguiaretic acid and esculetin. Zileuton and caffeic acid are used as 5-lipoxygenase inhibitors, while baicalein and CDC are 12-lipoxygenase inhibitors. The specificity of these inhibitors has not been rigorously assessed with all LOX forms: baicalein, along with other flavonoids, such as fisetin and luteolin, also inhibits 15-LOX-1 [14]. 2-TEDC is used as 5-, 12- and 15-LOX inhibitor [2].

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7. Jameson 2nd JB, Kantz A, Schultz L, Kalyanaraman C, Jacobson MP, Maloney DJ, Jadhav A, Simeonov A, Holman TR. (2014) A high throughput screen identifies potent and selective inhibitors to human epithelial 15-lipoxygenase-2. PLoS ONE, 9 (8): e104094. [PMID:25111178]

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Angelo A. Izzo Department of Pharmacy School of Medicine and Surgery University of Naples Federico II Naples, Italy