title: Targeting PI3K isoforms and SHIP in the immune system: new therapeutics for inflammation and leukemia.
abstract: PI3K is critical for the normal function of the immune system, however dysregulated PI3K mediated signaling has been linked to the development of many immune mediated pathologies. This review describes current progress in the development of isoform-specific PI3K inhibitors that hold promise for the treatment of hematopoietic malignancies as well as for inflammatory and autoimmune diseases. A SH2-domain containing inositol-5-phosphatase (SHIP) is a regulator of PI3K signaling, and is also discussed as a potential drug target for immunomodulation and the treatment of leukemia. Recent progress has been made in the development of small molecule compounds that potently and selectively modulate SHIP activity and hence provide a novel mechanism to alter PI3K mediated signaling.
authors.affiliation: Inflammatory Cell Biology Laboratory, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Blunt
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ward
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D000072181:Inositol Polyphosphate 5-Phosphatases; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D000072181:Inositol Polyphosphate 5-Phosphatases; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human