Isoforms of phospholipase D (PLD) cleave the head group from phospholipids, releasing the second messenger phosphatidic acid (PA), which can produce changes in Ras activation, cell spreading, stress fiber formation, chemotaxis, and membrane vesicle trafficking. FIPI is a derivative of halopemide which potently inhibits both PLD1 (IC50 = 25 nM) and PLD2 (IC50 = 20 nM). It also prevents PLD regulation of F-actin cytoskeleton reorganization, cell spreading, and chemotaxis. FIPI has good pharmacokinetic parameters in rats, with a half-life greater than five hours, a Cmax that, at 363 nM, is greater than 10-fold the IC50 versus PLD2, and bioavailability of 18%.
