5-Fluoro-2-indolyl des-chlorohalopemide (FIPI), a Phospholipase D Pharmacological Inhibitor That Alters Cell Spreading and Inhibits Chemotaxis

摘要: The signaling enzyme phospholipase D (PLD) and the lipid second messenger it generates, phosphatidic acid (PA), are implicated in many cell biological processes, including Ras activation, spreading, stress fiber formation, chemotaxis, membrane vesicle trafficking. PLD production of PA is inhibited by primary alcohol 1-butanol, which has thus been widely employed to identify PLD/PA-driven processes. However, 1-butanol does not always effectively reduce accumulation, its use may result PLD-independent deleterious effects. Consequently, identification potent specific small-molecule inhibitors would be an important advance for field. We examine one such here, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), was identified recently vitro chemical screen PLD2 inhibitors, show that rapidly blocks vivo with subnanomolar potency. were surprised find several processes blocked affected FIPI, suggesting need re-evaluation proposed roles PLD. FIPI inhibit regulation F-actin cytoskeleton reorganization, indicating potential utility as a therapeutic autoimmunity cancer metastasis.