ML355 is a potent and selective inhibitor of 12-Lipoxygenase (12-LOX) with an IC50 of 0.34 μM, shows excellent selectivity over related lipoxygenases and cyclooxygenases, and possesses favorable ADME properties. IC50: 0.34 μM (12-LOX)[1]
ML355 inhibits PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells[1].
ML355 (1.88-30 mg/kg; i.g.; 2 times per day for two days) strongly inhibits the thrombus formation in mice at higher dose compared to WT controls[3]. Animal Model: C57BL/6 mice[3]
[1]. Luci DK, et al. Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase. J Med Chem. 2014 Jan 23;57(2):495-506. [2]. Zhang XJ, et al. An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury. Nat Med. 2018 Jan;24(1):73-83. [3]. Adili R, et al. First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis. Arterioscler Thromb Vasc Biol. 2017 Oct;37(10):1828-1839.