Lipoxygenases (LOs) are non-heme iron-containing dioxygenases that catalyze the oxidation of polyunsaturated fatty acids to generate unsaturated fatty acid hydroperoxides. The immediate products of 15-LO fatty acid oxidation act as mediators in inflammation, thrombosis, and cancer. ML351 is an inhibitor of human reticulocyte 15-LO-1 (IC50 = 200 nM) with >250-fold selectivity over the related enzymes 5-LO, platelet 12-LO, 15-LO-2, ovine COX-1, and human COX-2. ML351 was shown to be protective against oxidative glutamate toxicity in mouse neuronal HT-22 cells and significantly reduced infarct size in an in vivo mouse model for ischemic stroke.
