Platelet-type 12-lipoxygenase (12-LO; ) catalyzes the formation of 12-HpETE from arachidonic acid . It has been found to be expressed in various tumor cells as well as pancreatic islets and can be activated by inflammatory cytokines. It has also been implicated in the modulation of hemostasis and thrombosis through its role in regulating platelet function. ML355 is a selective inhibitor of 12-LO with an IC50 value of 0.34 μM. It demonstrates greatly reduced potency for 15-LO-1, 15-LO-2, and 5-LO (IC50s = 9.7, >100, and >100 μM) and no inhibition of COX-1 and -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.
