Article ; Online: Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?
Annual review of pharmacology and toxicology
2023 Volume 63, Page(s) 617–636
Abstract: 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 ...
Abstract | 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. |
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MeSH term(s) | Humans ; Mitogen-Activated Protein Kinase Phosphatases/antagonists & inhibitors ; Neoplasms/drug therapy ; Protein Tyrosine Phosphatases/antagonists & inhibitors ; Protein Tyrosine Phosphatases/metabolism ; Signal Transduction ; Tyrosine Kinase Inhibitors/chemistry ; Tyrosine Kinase Inhibitors/pharmacology |
Chemical Substances | Mitogen-Activated Protein Kinase Phosphatases (EC 3.1.3.16) ; Protein Tyrosine Phosphatases (EC 3.1.3.48) ; Tyrosine Kinase Inhibitors |
Language | English |
Publishing date | 2023-03-21 |
Publishing country | United States |
Document type | Journal Article ; Review |
ZDB-ID | 196587-6 |
ISSN | 1545-4304 ; 0362-1642 |
ISSN (online) | 1545-4304 |
ISSN | 0362-1642 |
DOI | 10.1146/annurev-pharmtox-051921-121923 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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