12-Lipoxygenase: classification, possible therapeutic benefits from inhibition, and inhibitors.
The metabolism of arachidonic acid can be catalyzed by either one of two enzyme families; the cyclooxygenases or the lipoxygenases. The family of lipoxygenases is divided into four subtypes according to tissue distribution; 5-, 8-, 12-, and 15-lipoxygenase. 12-lipoxygenase metabolites, such as 12(S)-hydroxyeicosatetraenoic acid, have been found to play a central role in the various stages of the metastatic process in tumors and are, therefore, potential targets for anticancer treatment. A variety of lipoxygenase inhibitors already exist and can be classified into five major categories according to their mechanism of inhibition. These include antioxidants, iron chelators, substrate analogues, lipoxygenase-activating protein inhibitors, and, finally, epidermal growth factor-receptor inhibitors.
Dailey
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Institut für Pharmazeutische Chemie, Philipps-Universität, Marburg, 35032, Germany.
Imming
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D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000502:physiology; D001092:Arachidonate 12-Lipoxygenase / Q000145:classification* / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors; D009362:Neoplasm Metastasis
D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase