Discovery of novel protein tyrosine phosphatase sigma inhibitors through the virtual screening with modified scoring function

Protein tyrosine phosphatase sigma (PTPσ) is a promising target for the development of therapeutics for the neurological diseases caused by the impaired recovery from neural injury. Based on the virtual screening with the scoring function involving a new accurate solvation energy term and in vitro enzyme assay, we identified seven competitive PTPσ inhibitors with the associated IC50 values ranging from 5 to 11 μM. These inhibitors are structurally diverse and expected to have desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure–activity relationship studies to optimize the inhibitory activities against the neurological diseases. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of PTPσ are discussed in detail.