Phosphoinositide 3-kinase catalytic subunit (p110) isoforms (PI3K p110)

Phosphoinositide 3-kinase (PI3K) p110 isoforms are the catalytic subunits of Class I PI3Ks, which are essential lipid kinases that convert phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). This family consists of four isoforms—p110α, p110β, p110δ, and p110γ—which exhibit distinct expression patterns and physiological roles; for instance, p110α and p110β are ubiquitously expressed, while p110δ and p110γ are primarily found in leukocytes. These enzymes integrate signals from receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs) to regulate fundamental cellular processes such as growth, proliferation, survival, and metabolism via the AKT/mTOR pathway. Aberrant activation of PI3K signaling, often driven by PIK3CA mutations or PTEN deficiency, is frequently observed in a wide range of human cancers, making these isoforms high-priority therapeutic targets. Several isoform-selective inhibitors, such as alpelisib for p110α and idelalisib for p110δ, have been approved for clinical use, though their utility is often limited by class-specific toxicities like hyperglycemia and immune-mediated inflammation.

Other names

PI3K catalytic subunitsp110 alphap110 betap110 deltap110 gammaPIK3CAPIK3CBPIK3CDPIK3CGPhosphatidylinositol 3-kinase catalytic subunits

Competitive inhibition of the ATP-binding site of the p110 catalytic subunits, preventing the phosphorylation of PIP2 to PIP3 and thereby blocking the activation of downstream AKT/mTOR signaling pathways.