ML351 is a potent and selective inhibitor of human 15-lipoxygenase-1 with IC50 value of 200 nM [1][2].

Human lipoxygenases (LOX) are nonheme iron-containing enzymes that catalyze the dioxygenation of polyunsaturated fatty acids (e.g., linoleic acid (LA) and arachidonic acid (AA)) to form hydroperoxy fatty acids [1][2]. Human reticulocyte 15-lipoxygenase-1 is an attractive therapeutic target for its role in atherogenesis, diabetes, Alzheimer’s disease, new-born periventricular leukomalacia, breast cancer, and stroke [2].

ML351 is a potent and selective 15-lipoxygenase inhibitor. ML351 exhibited nanomolar potency and excellent selectivity (>250-fold) versus 5-LOX, platelet 12-LOX, 15-LOX-2, ovine COX-1, and human COX-2. In mouse neuronal HT22 cells, ML351 dose-dependently protected against oxidative glutamate toxicity and completely reversed the increase in 12-HETE following glutamate treatment [2][3].

In permanent focal ischemia mice model, IP administration of ML351 resulted in a ~30% reduction in infarct size [2][3].

References:
[1].  Rai G, Joshi N, Perry S, et al. Discovery of ML351, a Potent and Selective Inhibitor of Human 15-Lipoxygenase-1. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-2013 Apr 15 [updated 2014 Jan 13].
[2].  Rai G, Joshi N, Jung JE, et al. Potent and selective inhibitors of human reticulocyte 12/15-lipoxygenase as anti-stroke therapies. J Med Chem. 2014 May 22;57(10):4035-48.
[3].  Gaffney BJ. Lipoxygenases: structural principles and spectroscopy. Annu Rev Biophys Biomol Struct. 1996;25:431-59.