Protein tyrosine phosphatases (PTPs) are a large family of enzymes whose structural diversity and complexity rival those of protein tyrosine kinases (PTKs). This chapter summarizes and updates what is currently known about PTP inhibitors. Both specific and non-specific small molecule competitive and reversible PTP inhibitors are discussed. In addition, some examples of covalent and time-dependent PTP inactivators are also presented. Although all PTPs share a common catalytic mechanism and catalyze the same biochemical reaction, the hydrolysis of phosphoamino acids, they have distinct (and often unique) biological functions in vivo. Genetics and biochemical studies indicate that PTPs are involved in a number of disease processes. In spite of the large number of PTPs identified to date, and the emerging roles played by PTPs in human diseases, a detailed understanding of the role played by PTPs in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific agents. Such PTP specific inhibitors could potentially serve as useful tools in determining the physiological significance of protein tyrosine phosphorylation in complex cellular signal transduction pathways, and may constitute valuable therapeutics in the treatment of several human diseases. Significant differences exist within the active site and its immediate surroundings of various PTPs, such that selective, tight-binding PTP inhibitors can be developed. Combinatorial solid-phase library synthesis is finding wide applicability throughout the pharmaceutical industry and has begun to yield fruitful results in the area of PTP inhibitors.
|Original language||English (US)|
|Title of host publication||Handbook of Cell Signaling, 2/e|
|Number of pages||9|
|State||Published - Dec 1 2010|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)