Kinases, as key members of the enzyme family, catalyze the transfer of the γ-phosphate group from ATP or GTP to specific amino acid residues on substrates, thereby inducing phosphorylation (Figures 1-2).

Figure 1. Generic catalytic domain of protein kinases depicting subdomain structure and function (Lahiry P, et al, Nat Rev Genet, 2010)

Figure 2.  Phospho-signaling networks. The mechanism of phosphorylation regulation consists of kinases, phosphatases and their substrates phospho-binding proteins.  (Ardito F, et al., Int J Mol Med. 2017)

Protein kinases are integral to cellular signaling pathways and they play a key role in the regulation of cell apoptosis, cell cycle progression, angiogenesis, and cellular metabolism. They serve as vital targets across a range of therapeutic areas, including cancer immunotherapy, inflammatory and cardiovascular disease. To date, the FDA has approved over 80 small-molecule kinase inhibitors (SMKIs), targeting 21 kinase families and covering approximately 20% of the known kinome.

Mutant kinases, often associated with acquired drug resistance, have become critical targets in drug discovery and development. Addressing mutation-driven resistance remains a critical unmet clinical need, making the comprehensive study of kinases and their mutants, along with the targeted screening and optimization of small-molecule inhibitors, a cornerstone in advancing cancer treatment.