A protein kinase inhibitor is a type of enzyme inhibitor that can block the action of protein kinases. Protein kinases add a phosphate group to a protein in a process called phosphorylation, which can turn a protein on or off and therefore affect its level of activity and function.
Protein kinase inhibitors can be subdivided according to the amino acid on a protein that they add the phosphate to (e.g serine, threonine or tyrosine) in order to inhibit phosphorylation of that amino acid. Kinases mostly act on both serine and threonine, but tyrosine kinase acts on tyrosine only and some dual-specificity kinases act on all three of these amino acid residues. Some protein kinases also phosphorylate other amino acids, such as histidine kinases that act on histidine residues.
Phosphorylation is often a required step in the growth of some cancers and inflammatory disorders, meaning inhibition of the enzymes that trigger phosphorylation provides an approach to treating such diseases.
One example of a drug being used in this way is the tyrosine kinase inhibitor dasatinib, which is used as an anticancer therapy in several forms of leukemia. Another agent currently being tested in clinical trials for polycystic kidney disease is PLX5568.
Tyrosine kinase inhibitors are particularly important agents because these high-affinity cell surface receptors play a critical role in the progression of many cancers.
Tyrosine kinases are involved in various cell functions including cell signalling, cell growth and cell division. In some forms of cancer, these enzymes are present in high levels or overactive and inhibiting them can prevent the proliferation of cancer cells. Tyrosine kinase inhibitors therefore provide an important form of targeted therapy in the fight against cancer.