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

Receptor protein tyrosine phosphatase sigma (PTPσ) 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 PTPσ. These inhibitors revealed high potencies with the associated IC(50) values ranging from 0.1 to 1.3 μM 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 PTPσ are discussed in detail.