Onvoloxastat

Onvoloxastat (ML355) is an orally active selective 12-LOX inhibitor with an IC₅₀ of 0.34 μM. Onvoloxastat 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 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) 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) inhibits fibrinogen binding in a time-dependent manner in washed human platelets^[1].
Onvoloxastat (1-50 μM; 30 min) 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) does not directly affect cGMP-producing activity in recombinant human GC-1 enzyme^[1].
Onvoloxastat (25-100 μM; 5 min) 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) attenuates platelet adhesion, aggregation and thrombosis in human whole blood^[2].
Onvoloxastat (1 pM-100 μM; 4 h) inhibits AA/IONO-stimulated 12-HETE production in mouse pancreatic islet β cells (BTC3)^[3].
Onvoloxastat (10 μM; 30 min) inhibits AA/IONO-induced 12-HETE expression in human primary islet cells^[3].
Onvoloxastat (1-50 μM; 30 min) 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) 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) 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) 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) 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) 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) 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) 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) 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) does not significantly prolong tail bleeding time or increase total red blood cell loss in the tail amputation bleeding model of WT mice^[2].