| Autor: |
Shillingford SR; Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; email: anton.bennett@yale.edu.; Department of Chemistry, Yale University, New Haven, Connecticut, USA., Bennett AM; Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; email: anton.bennett@yale.edu.; Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, Connecticut, USA. |
| Abstrakt: |
Phosphatases and kinases maintain an equilibrium of dephosphorylated and phosphorylated proteins, respectively, that are required for critical cellular functions. Imbalance in this equilibrium or irregularity in their function causes unfavorable cellular effects that have been implicated in the development of numerous diseases. Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of protein substrates on tyrosine residues, and their involvement in cell signaling and diseases such as cancer and inflammatory and metabolic diseases has made them attractive therapeutic targets. However, PTPs have proved challenging in therapeutics development, garnering them the unfavorable reputation of being undruggable. Nonetheless, great strides have been made toward the inhibition of PTPs over the past decade. Here, we discuss the advancement in small-molecule inhibition for the PTP subfamily known as the mitogen-activated protein kinase (MAPK) phosphatases (MKPs). We review strategies and inhibitor discovery tools that have proven successful for small-molecule inhibition of the MKPs and discuss what the future of MKP inhibition potentially might yield. |
