|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Zheng, W, Brandish, PE, D Kolodin, G, Scolnick, EM, Strulovici, B|
|Journal||J Biomol Screen|
|Date Published||2004 Mar|
|Keywords||Atropine, Biological Assay, Carbachol, Cells, Cultured, Chromatography, High Pressure Liquid, Humans, Models, Biological, Phosphoric Monoester Hydrolases, Scintillation Counting|
Inositol monophosphatase is a potential drug target for developing lithium-mimetic agents for the treatment of bipolar disorder. Enzyme-based assays have been traditionally used in compound screening to identify inositol monophosphatase inhibitors. A cell-based screening assay in which the compound needs to cross the cell membrane before reaching the target enzyme offers a new approach for discovering novel structure leads of the inositol monophosphatase inhibitor. The authors have recently reported a high-throughput measurement of G-protein-coupled receptor activation by determining inositol phosphates in cell extracts using scintillation proximity assay. This cell-based assay has been modified to allow the determination of inositol monophosphatase activity instead of G-protein-coupled receptors. The enzyme is also assayed in its native form and physiological environment. The authors have applied this cell-based assay to the high-throughput screening of a large compound collection and identified several novel inositol monophosphatase inhibitors.
|Alternate Journal||J Biomol Screen|