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

ABSTRACT:

Background and purpose

The lipid phosphatase known as SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) plays an important role in the regulation of the intracellular insulin signalling pathway. Recent studies have suggested that inhibition of SHIP2 could produce significant benefits in treatment of type 2 diabetes. However, there were no small molecule SHIP2 inhibitors 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 pharmacological profiles of suitable compounds were further characterized in phosphatase assays, cellular assays and oral administration in normal and diabetic (db/db) mice.

Key results

During high-throughput screening, AS1949490

SUBMITTER: Suwa A 

PROVIDER: S-EPMC2765606 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature