Substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase.

ABSTRACT: High levels of striatal-enriched protein tyrosine phosphatase (STEP) activity are observed in a number of neuropsychiatric disorders such as Alzheimer's disease. Overexpression of STEP results in the dephosphorylation and inactivation of many key neuronal signaling molecules, including ionotropic glutamate receptors. Moreover, genetically reducing STEP levels in AD mouse models significantly reversed cognitive deficits and decreased glutamate receptor internalization. These results support STEP as a potential target for drug discovery for the treatment of Alzheimer's disease. Herein, a substrate-based approach for the discovery and optimization of fragments called substrate activity screening (SAS) has been applied to the development of low molecular weight (<450 Da) and nonpeptidic, singl

SUBMITTER: Baguley TD 

PROVIDER: S-EPMC3875168 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature