RESEARCH PAPER Discovery and functional characterization of a novel small molecule inhibitor of the intracellular phosphatase, SHIP2

Background and purpose: The lipid phosphatase known as SH2 domain-containing inositol 5′-phosphatase 2 (SHIP2) playsan important role in the regulation of the intracellular insulin signalling pathway. Recent studies have suggested that inhibitionof SHIP2 could produce significant benefits in treatment of type 2 diabetes. However, there were no small molecule SHIP2inhibitors and we, therefore, aimed to identify this type of compound.Experimental approach: The phosphatase assay with malachite green was used for high-throughput screening. The phar-macological profiles of suitable compounds were further characterized in phosphatase assays, cellular assays and oral admin-istration in normal and diabetic (