Platelet-type 12-lipoxygenase catalyzes the formation of 12-HpETE from arachidonic acid .1 It has been found to be expressed in various tumor cells as well as pancreatic islets and can be activated by inflammatory cytokines.2 It has also been implicated in the modulation of hemostasis and thrombosis through its role in regulating platelet function.2 ML355 is a selective inhibitor of 12-LO with an IC50 value of 0.34 ?M.2 It demonstrates greatly reduced potency for 15-LO-1, 15-LO-2, and 5-LO (IC50s = 9.7, >100, and >100 ?M) and no inhibition of COX-1 and -2.2 In cell-based assays, ML355 has been shown to decrease calcium mobilization and thrombin receptor PAR4-induced platelet aggregation in patient-derived human platelets and to significantly inhibit arachidonic acid and calcium- ionophore-induced 12-HpETE synthesis in mouse BTC3 cells and human islets.2
1.Chen, X.-S., Kurre, U., Jenkins, N.A., et al.cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenasesJ. Biol. Chem.269(19)13979-13987(1994) 2.Luci, D.K., Jameson, J.B., II, Yasgar, A., et al.Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenaseJ. Med. Chem.57(2)495-506(2014)