Virtual Screening and Biochemical Evaluation of Mitogen-activated Protein Kinase Phosphatase 4 Inhibitors

Abstract

Mitogen-activated protein kinase phosphatase 4 (MKP4) has proved to be a promising target for the development of therapeutics for the treatment of diabetes and the other metabolic diseases. Here, we report an example for a successful application of the structure-based virtual screening to identify three novel inhibitors of MKP4. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with <TEX>$IC_{50}$</TEX> values ranging from 4.9 to <TEX>$32.3{\mu}M$</TEX>. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize the inhibitory and antidiabetic activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of MKP4 are discussed in detail.