Multiple protein kinases (PKs)

Multiple protein kinases represent a diverse group of enzymes that catalyze the transfer of phosphate groups from ATP to specific amino acid residues on substrate proteins. This phosphorylation serves as a fundamental regulatory mechanism for signal transduction, controlling nearly every aspect of cellular life, including growth, division, and death (Manning et al., 2002). In a clinical and pharmacological context, this term is often used to describe the collective targets of multikinase inhibitors (MKIs), which are small molecules designed to block several signaling pathways at once (Wilhelm et al., 2006). These drugs typically target a combination of receptor tyrosine kinases, such as VEGFR and PDGFR, and intracellular kinases like RAF or KIT, to inhibit both tumor cell proliferation and the formation of new blood vessels (Broekman et al., 2011). Because these kinases are also involved in normal physiological processes, their broad inhibition can lead to significant systemic toxicities, such as hypertension and skin reactions (Force & Kolaja, 2011). Despite these challenges, targeting multiple kinases remains a cornerstone of treatment for various solid tumors, including renal cell carcinoma and hepatocellular carcinoma, where redundant signaling pathways often drive resistance to more selective agents (Gotink & Verheul, 2010).

Other names

MultikinaseProtein kinase familyKinomeMultiple kinases

Inhibition of ATP binding to the catalytic domain of multiple protein kinases, preventing substrate phosphorylation and downstream signaling (Manning et al., 2002).