Abstract: Protein tyrosine phosphatases (PTPs) are implicated in a number of disease processes, including autoimmune diseases, glucose intolerance, diabetes, obesity and certain types of proliferative diseases such as cancer and psoriasis. The present invention discloses novel &agr;-ketocarboxylic acid inhibitors of PTPs, methods for synthesizing said inhibitors, and methods for using pharmaceutical compositions of the inhibitors to treat PTP-mediated disorders, diseases or dysfunctions. The compositions described herein can also be used as diagnostic and screening tools to elucidate complex signal transduction pathways involving PTPs or to identify PTP-mediated disease states.