title: Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development.
abstract: Several 'classical' protein tyrosine phosphatases are attractive therapeutic targets, including PTP1B for obesity and Type II diabetes; SHP2 for cancer and Lyp for rheumatoid arthritis. Progress has been made in identifying a broad range of chemically distinct inhibitors; however, developing selective and cell-permeable clinically useful compounds has proved challenging. Here the ongoing challenges and recent significant advances in the field are reviewed. Key novel compounds are highlighted and a perspective on the future of phosphatase inhibitor development is presented.
authors.affiliation: University of Oxford, Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK. alastair.barr@sgc.ox.ac.uk
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Barr
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases