Secreted phospholipase A2 (sPLA2) (sPLA2)

Secreted phospholipase A2 (sPLA2) is a family of extracellular enzymes that catalyze the hydrolysis of the sn-2 ester bond of phospholipids, producing lysophospholipids and free fatty acids such as arachidonic acid [1][3]. These enzymes play a pivotal role in the inflammatory response by providing the precursors for eicosanoid biosynthesis, including prostaglandins and leukotrienes [4]. Elevated levels of sPLA2, particularly the Group IIA isoform, are linked to chronic inflammatory conditions, atherosclerosis, and acute coronary syndromes [1][2]. Therapeutic development has focused on small-molecule inhibitors like varespladib to block sPLA2 activity and mitigate inflammation [2]. However, clinical trials have encountered significant hurdles, including a lack of efficacy in reducing cardiovascular events and, in some cases, an increased risk of myocardial infarction, leading to the discontinuation of several drug candidates [2][4]. The term "enzymatic substrates" in the provided name is technically incorrect as it refers to the molecules acted upon by the enzyme rather than the therapeutic target itself. Despite these challenges, sPLA2 remains a subject of research due to its diverse roles in host defense and lipid signaling [3]. Understanding the isoform-specific functions of sPLA2 is crucial for developing more selective and safer therapeutic interventions [1].

Other names

sPLA2Group IIA phospholipase A2PLA2G2APhosphatidylcholine 2-acylhydrolaseNon-pancreatic secretory phospholipase A2

Inhibition of the sPLA2 enzyme active site to prevent the hydrolysis of phospholipids and the subsequent release of pro-inflammatory fatty acids and lysophospholipids.