title: Using small molecules to target protein phosphatases.
abstract: The site specific functionalization of phosphate groups with amino acid side chains of substrate proteins represents one of the most important regulatory mechanisms of biological systems. Phosphorylation and dephosphorylation are reversibly catalyzed by protein kinases and protein phosphatases, and the aberrant regulation of these enzymes is associated with the onset and progression of various disease states such as cancer, diabetes, neurodegenerative and autoimmune disorders, making these proteins attractive targets for drug discovery. Here we report on strategies currently explored for the identification and development of various inhibitors directed against clinically relevant phosphatases. While over the last years, inhibition of phosphorylation has evolved into a key strategy in targeted therapies, the development of clinically relevant phosphatase inhibitors still faces major bottlenecks and is often plagued by limited selectivity and unfavorable pharmacokinetics. The reader will gain a better understanding of the importance of the field and its current limitations.
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Vintonyak
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases