Small-molecule inhibitors as potential therapeutics and as tools to understand the role of phospholipases A₂.

ABSTRACT: Phospholipase A₂ (PLA₂) enzymes are involved in various inflammatory pathological conditions including arthritis, cardiovascular and autoimmune diseases. The regulation of their catalytic activity is of high importance and a great effort has been devoted in developing synthetic inhibitors. We summarize the most important small-molecule synthetic PLA₂ inhibitors developed to target each one of the four major types of human PLA₂ (cytosolic cPLA₂, calcium-independent iPLA_2, secreted sPLA_2, and lipoprotein-associated LpPLA₂). We discuss recent applications of inhibitors to understand the role of each PLA₂ type and their therapeutic potential. Potent and selective PLA₂ inhibitors have been developed. Although some of them have been evaluated in clinical trials, none reached the market yet. Apart from their importance as potential medicinal agents, PLA₂ inhibitors are excellent tools to unveil the role that each PLA₂ type plays in cells and in vivo. Modern medicinal chemistry approaches are expected to generate improved PLA₂ inhibitors as new agents to treat inflammatory diseases.

SUBMITTER: Nikolaou A 

PROVIDER: S-EPMC7106526 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature