| Description: | Human lysosomal phospholipase A2 (LPLA2) is responsible for normal lipid metabolism and it is unique from other known PLA2s in that LPLA2 is only active in an acidic environment (~pH 4.5). Phospholipidosis (PL) is a condition resulting from the excessive accumulation of intracellular phospholipids, causing tissue inflammation and organ damage. PL can manifest in patients taking certain cationic amphiphilic drugs (CADs) such as fluoxetine (Prozac?, Sarafem) and Amiodarone. The FDA has determined that drug-induced phospholipidosis (DIPL) is a serious drug safety issue and evidence is accumulating that DIPL is the result of certain CADs directly inhibiting LPLA2. Echelon’s LPLA2 Inhibitor Screen (K-7000I) is designed to assay a drug’s ability to inhibit LPLA2 activity in vitro, and thus potentially predict DIPL. The assay uses a quenched substrate which fluoresces when hydrolyzed by LPLA2. This direct biochemical approach provides a quantitative measurement in a robust and simple-to-use in vitro plate-based assay, providing greatly increased throughput when compared to traditional microscopy methods of tissue cultured cells. The assay has been validated with a group of known PL-inducing and non-PL inducing drugs. The known PL-inducing cationic amphiphilic drug, amiodarone, is included in the assay as a control. |
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