Onvoloxastat (ammonium)

Onvoloxastat ammonium (ML355 ammonium) is an orally active selective 12-LOX inhibitor with an IC₅₀ of 0.34 μM. Onvoloxastat ammonium inhibits platelet activation by blocking thrombin- or thromboxane A2-induced phosphorylation of Akt, PI3K and Erk1/2. At low doses (1-20 μM), it mainly acts by reducing ROS levels, while at high doses (50 μM), it functions via activating the cAMP pathway. Onvoloxastat ammonium can be used in research related to thrombosis and diabetes^[1][2][3][4]. IC50 & Target:IC50: 0.34 μM (12-LOX)^[1] In Vitro:Onvoloxastat (ML355) (1-50 μM; 40 min) ammonium dose-dependently inhibits αIIbβ3 integrin activation in washed human platelets induced by Thrombin (HY-114164) and U46619 (HY-108566)^[1].
Onvoloxastat (50 μM; 1-60 min) ammonium inhibits fibrinogen binding in a time-dependent manner in washed human platelets^[1].
Onvoloxastat (1-50 μM; 30 min) ammonium induces cAMP-dependent phosphorylation of VASP at Ser157 and Ser239 in washed human platelets without affecting cell viability^[1].
Onvoloxastat (0.1-100 μM; 10 min) ammonium does not directly affect cGMP-producing activity in recombinant human GC-1 enzyme^[1].
Onvoloxastat (25-100 μM; 5 min) ammonium dose-dependently inhibits platelet aggregation induced by Thrombin, PAR1-AP, PAR4-AP (HY-P1309) and Collagen (HY-NP003), and reduces 12-HETE production in washed human platelets^[2].
Onvoloxastat (25-100 μM; pre-incubated for 5 min) ammonium attenuates platelet adhesion, aggregation and thrombosis in human whole blood^[2].
Onvoloxastat (1 pM-100 μM; 4 h) ammonium inhibits AA/IONO-stimulated 12-HETE production in mouse pancreatic islet β cells (BTC3)^[3].
Onvoloxastat (10 μM; 30 min) ammonium inhibits AA/IONO-induced 12-HETE expression in human primary islet cells^[3].
Onvoloxastat (1-50 μM; 30 min) ammonium dose-dependently blocks the phosphorylation of Akt, PI3K and Erk1/2 and reduces reactive oxygen species (ROS) levels in thrombin-activated washed human platelets, but does not affect p38 phosphorylation. It does not inhibit platelet activation in Crp-XL-activated washed human platelets^[1].
Onvoloxastat (1-50 μM; 60 min) ammonium dose-dependently inhibits ABT-737 (HY-50907)-induced phosphatidylserine (PS) externalization and Caspase-3 cleavage in washed human platelets^[1]. In Vivo:Onvoloxastat (ML355) (1.5 mg/kg; i.v.; single dose; 24 h pretreatment) ammonium delays vascular occlusion in the FeCl₃ (HY-Y0266)-induced carotid artery thrombosis model^[1].
Onvoloxastat (1.5 mg/kg; i.v.; single dose; 24 h pretreatment) ammonium inhibits platelet recruitment and thrombus growth in a laser-induced cremaster muscle microartery thrombosis model^[1].
Onvoloxastat (1.5 mg/kg; i.v.; single administration; 24 h pre-treatment) ammonium does not impair normal hemostatic function, prolong bleeding time, or increase blood loss in the tail-clip bleeding model and thromboelastography assay^[1].
Onvoloxastat (15-30 mg/kg; i.g.; twice daily; for 2 consecutive days) ammonium inhibits thrombus growth and significantly delays the time to complete vascular occlusion in a ferric chloride FeCl₃-induced mesenteric arteriolar thrombosis model in wild-type mice^[2].
Onvoloxastat (1.88-30 mg/kg; i.g.; twice daily; for 2 consecutive days) ammonium potently inhibits thrombosis in a laser-induced cremasteric arteriole thrombosis model in WT mice^[2].
Onvoloxastat (15 mg/kg; i.g.; twice daily; for 2 consecutive days; recorded for 5 minutes after laser injury, with repeated injuries at 5- and 10-minute intervals) ammonium exerts no significant effect on hemostatic plug formation and platelet plug dynamics in the laser-ablated saphenous vein hemostasis model of WT mice^[2].
Onvoloxastat (15 mg/kg; i.g.; twice daily; for 2 consecutive days) ammonium does not alter microvascular hemostasis time in laser-induced cremaster muscle microvascular rupture and plasma extravasation models of WT mice^[2].
Onvoloxastat (3.5-30 mg/kg; i.g.; twice daily; for 2 consecutive days) ammonium does not significantly prolong tail bleeding time or increase total red blood cell loss in the tail amputation bleeding model of WT mice^[2].