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lüll Phosphatase-resistant analogues of lysophosphatidic acid: agonists promote healing, antagonists and autotaxin inhibitors treat cancer Prestwich GD; Gajewiak J; Zhang H; Xu X; Yang G; Serban MBiochim Biophys Acta 2008[Sep]; 1781 (9): 588-94Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G protein-coupled receptors (GPCRs) have important potential applications in cell biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion, angiogenesis, and also biochemical resistance to chemotherapy- and radiotherapy-induced apoptosis. LPA and its analogues also are feedback inhibitors of the enzyme lysophospholipase D (lysoPLD, a.k.a., autotaxin, ATX), a central regulator of invasion and metastasis. For cancer therapy, the optimal therapeutic profile would be a metabolically-stabilized, pan-LPA receptor antagonist that also inhibited lysoPLD. For protection of gastrointestinal mucosa and lymphocytes, LPA agonists would be desirable to minimize or reverse radiation or chemical-induced injury. Analogues of lysophosphatidic acid (LPA) that are chemically modified to be less susceptible to phospholipases and phosphatases show activity as long-lived receptor-specific agonists and antagonists for LPA receptors, as well as inhibitors for the lysoPLD activity of ATX.|Animals[MESH]|Enzyme Inhibitors/chemistry/*pharmacology[MESH]|Humans[MESH]|Lysophospholipids/*metabolism[MESH]|Neoplasms/*enzymology/pathology[MESH]|Phosphoric Monoester Hydrolases/*antagonists & inhibitors/metabolism[MESH]|Pyrophosphatases/*antagonists & inhibitors/metabolism[MESH]|Wound Healing/*drug effects[MESH] |