Phospholipase is a member of a very complex group of enzymes that break down phospholipids into fatty acids and other compounds. Phospholipase is defined by the enzymatic reaction they catalyze. The classes are phospholipase A, which has members A1 and A2; phospholipase B, which can carry out the reactions of both A1 and A2; phospholipase C; and phospholipase D.
Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins (PGs) and leukotrienes (LTs). PLA2 enzymes commonly exit in mammalian tissues as well as arachnid, insect, and snake venom. The phospholipase A2 (PLA2) enzyme superfamily includes 4 major types, including secreted sPLA2, cytoplasmic cPLA2, calcium-independent iPLA2, and platelet-activating factor (PAF) acetylhydrolase/oxidized lipid lipoprotein-associated (Lp) PLA2. Inhibition of PLA2 has also been reported to be associated with neuroinflammation similar to Alzheimer’s disease, epilepsy, multiple sclerosis, ischemia, and other neurological diseases. In addition to this, PLA2 has become a major drug target for many different diseases.
Fuzapladib (IS-741) is a potent phospholipase A2 inhibitor.
Fuzapladib (IS-741) is a potent phospholipase A2 inhibitor. It can block the adhesion of inflammatory cells to microvascular endothelial cells. And Fuzapladib can inhibit the infiltration of neutrophils into the pancreas or acute pancreatitis. Also, it has anti-acute pancreatitis effects. According to reports, Fuzapladib(IS-741)(1 μM, 3 h) can significantly inhibit the adhesion of HL-60 cells to HUVEC under the stimulation of lipopolysaccharide. Besides, Fuzapladib (IS-741) (p.o., 50 mg/kg, 7 days) significantly reduces myeloperoxidase (MPO) activity and mucosal IL-8 levels in rat ileum, reduces polymorphonuclear cells and Mac-1 positivity Infiltration of cells into inflammatory lesions effectively alleviates trinitrobenzene sulfonic acid (TNBS)-induced ileitis in rats.
In conclusion, Fuzapladib (IS-741) is a potent PLA2 inhibitor for inflammatory disease research.