Kinases and G protein-coupled receptors (GPCRs) (Kinases / GPCRs)

Kinases and G protein-coupled receptors (GPCRs) represent the two most significant and clinically relevant superfamilies of therapeutic targets in the human genome (Santos et al., 2017). Kinases are enzymes that regulate a vast array of cellular processes by catalyzing the transfer of phosphate groups to specific substrates, acting as molecular switches for signaling pathways involved in growth, differentiation, and metabolism (Manning et al., 2002). GPCRs are integral membrane proteins that transmit extracellular signals into the cell by activating heterotrimeric G proteins, mediating responses to hormones, neurotransmitters, and environmental stimuli (Hauser et al., 2017). Together, these families are involved in nearly every aspect of human physiology, and their dysregulation is a primary driver of diseases such as cancer, diabetes, and heart failure. Drug development for these targets includes a wide range of small molecules and biologics, though achieving high selectivity remains a significant challenge due to the structural similarities shared among family members (Insel et al., 2007). Despite these hurdles, they remain the focus of intense research and account for a significant portion of the current pharmacopeia.

Other names

Protein kinases7-transmembrane receptors7TM receptorsPhosphotransferasesGPCRs

Kinase inhibitors typically function through competitive inhibition of the ATP-binding site or allosteric modulation to prevent protein phosphorylation (Roskoski, 2021). GPCR-targeted drugs act as agonists, antagonists, or inverse agonists to modulate intracellular signaling cascades via G proteins or beta-arrestins (Hauser et al., 2017).