Proteases and Protein Kinases as Potential Drug Target

Recently, the successful pharmacological targeting of protein and phosphoinositide kinases has been applied to a wide range of diseases, most notably cancer, immune deficiencies, viral infection, and neurodegenerative disease leading to the successful clinical development of effective and selective inhibitors of phosphoinositide kinases. However, targeting of phosphoinositide kinases is most effective for plasmodium to treat malaria. The phosphatidylinositol 4-kinase (a key member from family of phosphoinositide) type III beta (PI4KIII) is now in phase-2 clinical research as a possible therapeutic target for treatment of malaria. Golgi and trans-Golgi network (TGN) membranes control the cellular regulation and trafficking throughout the Golgi apparatus and are well defined by PI4KII. In this perspective, here in this chapter we discuss the promise of kinases as therapeutic targets for antimalarial drugs, efficiencies, and challenges. Many parasites depend on kinases for various physiological activities, and these enzymes are easily targeted with drugs provided. By virtue of strong conserved nature of all binding sites from ATP molecules, it is difficult to find Plasmodium kinase inhibitors (K+ inhibitor) that are selective against mammalian (human) ortholog(s) and other human kinase enzymes. Despite the numerous significant differences between the Plasmodium and human kinomes, these variations are leveraged to our benefit in drug targeting and the development of resistance to multiple drugs. There is also the possibility of using other medicine and pharmacological products that inhibit multiple plasmodium kinases which come under the subject of polypharmacology. It is crucial to evaluate prospective about kinase targets before beginning the drug discovery to ensure that the desired kinase inhibition would kill the parasites in important phase of their life cycle at faster rate within short period of time. In this publication, we focus on the critical drug target (PI4KIII) for the development of novel and innovative drugs to treat malaria, cGMP-dependent protein kinase, cyclin-dependent-like kinase and summarize the overall progress about targeting of proteins.