title: The phospholipase D superfamily as therapeutic targets.
abstract: The phospholipase D (PLD) lipid-signaling enzyme superfamily has long been studied for its roles in cell communication and a wide range of cell biological processes. With the advent of loss-of-function genetic mouse models that have revealed that PLD1 and PLD2 ablation is overtly tolerable, small-molecule PLD1/2 inhibitors that do not cause unacceptable clinical toxicity, a PLD2 polymorphism that has been linked to altered physiology, and growing delineation of processes that are subtly altered in mice lacking PLD1/2 activity, the stage is being set for assessment of PLD1/2 inhibition for therapeutic purposes. Based on findings to date, PLD1/2 inhibition may be of more utility in acute rather than chronic settings, although this generalization will depend on the specific risks and benefits in each disease setting.
authors: Department of Pharmacological Sciences and the Center for Developmental Genetics, 438 Centers for Molecular Medicine, Stony Brook University, Stony Brook, NY 11794-5140, USA. Electronic address: Michael.Frohman@stonybrook.edu.
authors: Michael A
authors: MA
authors: Frohman
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007251:Influenza, Human / Q000188:drug therapy; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D010739:Phospholipase D / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D007527:Isoenzymes; D010739:Phospholipase D
keywords: PLD1; PLD2; autoimmune disease; cancer; small-molecule inhibitors; thrombosis