Table 2 Tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKIs) are a group of drugs that disrupt the tyrosine kinase (TK) signal transduction pathway through a variety of mechanisms. They can compete with adenosine triphosphate (ATP), phosphorylated entities, substrates, or can act in an allosteric manner, that is, bind to sites outside the active site and affect the sites’ activity through conformational changes. TKs can be divided into receptor tyrosine kinases (RTKs), nonreceptor tyrosine kinases (NRTKs), and dual-specific kinases (DSKs). DSKs phosphorylate serine, threonine, and tyrosine residues. Approximately 20 different transmembrane RTK subfamilies have been identified, such the families for vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), insulin receptor (INSR), fibroblast growth factor receptor (FGFR), and epidermal growth factor receptor (EGFR). NRTKs are cytoplasmic proteins and do not have a transmembrane domain. NRTKs are mainly composed of nine families, including those for Abl, Ack, Csk, Fak, Fes/Fer, Jak, Src, Syk/Zap70, and Tec. The most typical example of DSK is mitogen-activated protein kinase kinase (MEK), which is involved in the mitogen-activated protein kinase (MAPK) pathway. More than 50 FDA-approved TKIs (including small-molecule inhibitors and monoclonal antibodies) are used to treat various diseases, including cancer.