Discovery of potent inhibitors of receptor protein tyrosine phosphatase sigma through the structure-based virtual screening

Abstract

Receptor protein tyrosine phosphatase sigma (PTP sigma) has proved to be a promising target for the development of therapeutics for the treatment of neurological diseases. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule inhibitors of PTP sigma. These inhibitors revealed high potencies with the associated IC50 values ranging from 0.1 to 1.3 mu M and were also screened for having desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure-activity relationship studies to develop therapeutics for neurological diseases. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of PTP sigma are discussed in detail.