Chapter 3 - Drug discovery for cancer therapy with special reference to inhibitors of protein kinase pathway

Abstract

The protein kinases execute a wide range of cellular processes, such as metabolism, cell cycle regulation, differentiation, proliferation, transcription, survival, migration, and apoptosis. Protein kinase transfers the phosphate group from adenosine triphosphate (ATP) to the hydroxyl group of the serine, threonine, and/or tyrosine residues of a particular substrate. Genetic alterations of protein kinase affect the function of kinases, leading to the development of various human diseases such as cardiovascular, inflammatory, autoimmune, nervous diseases, and cancer. Significantly, kinases are placed at the second-most targeted proteins after G-protein-coupled receptors. Above 60 kinase-specific small molecules are approved by the FDA, targeting 50 out of 538 different kinases. Furthermore, more than 50–60 compounds are in the preclinical stage targeting another 15–20 different kinases. This chapter summarizes protein kinases, their classification, structure, regulation, and involvement in cancer progression. Additionally, it also discussed the present protein kinase drugs approved by FDA, their challenges, and future perspectives.