Cancers are characterized by uncontrolled cell growth, increased cell survival, remodeling of tumor microenvironment, neovascularization, invasion and metastasis. Each of these processes involves perturbation of key regulatory pathways. Disruption of these pathways is often caused by mutations and modifications in proteins that occupy hub positions, resulting in either disruption of their function or aberrant activation. Protein kinases are an excellent example of a class of enzymes whose activity if often found to be deregulated in diseases including cancers [1, 2]. Protein kinases mediate the covalent addition of phosphate group to amino acid side chains in proteins thereby modifying them post-translationally. The hydroxyl groups of serine, threonine, tyrosine or histidine amino acid side chains are the most common phosphoacceptor sites on proteins. Reversible protein phosphorylation plays an important role in essentially every aspect of life including cellular processes that mediate metabolism, cell cycle progression, proliferation, apoptosis, differentiation, cytoskeletal dynamics, cell migration, immune response, and intracellular transport.

Recent technological advances have enabled rapid identification of downstream targets of protein kinases deregulated in cancer [3, 4]. Aberrant protein phosphorylation has been observed in many human cancers and has been shown to affect the stability and function of key oncogenes and tumor suppressors [5-8]. Although protein kinases have emerged as attractive druggable anti-cancer targets, successful selective targeting of protein kinases has proven difficult. A major impediment has been off-target effects of the many extant small molecule protein kinase inhibitors. This stems from the fact that the catalytic fold of different protein kinases, which is often the target for rational drug design share significant structural similarity with each other. Interestingly, many protein kinases use additional protein-protein interaction domains to establish specific kinase-substrate interaction in addition to the target site preferences on substrates defined by stereochemical complementarity with active site. For instance, the SH2 and SH3 domains in tyrosine kinases have been shown to be important in substrate binding [9]. Several Ser/Thr protein kinases including Cyclin-dependent kinases (CDKs), Mitogen activated protein kinases (MAPK), Polo-like Kinase 1 (PLK1), 3-phosphoinositide-dependent kinase-1 (PDK1) and Glycogen Synthase Kinase 3ß (GSK3ß) possess additional docking domains, which are important in substrate recruitment [10-12].