Class I Phosphatidylinositol 3-kinase (PI3K class I)

Class I Phosphatidylinositol 3-kinases (PI3Ks) are essential lipid kinases that regulate a wide array of cellular processes, including growth, proliferation, survival, and intracellular trafficking (PMID: 30447065). These enzymes function as heterodimers composed of a catalytic p110 subunit (α, β, δ, or γ) and a regulatory subunit. The p110α isoform, encoded by the PIK3CA gene, is one of the most frequently mutated oncogenes in human cancer, particularly in breast, endometrial, and colorectal malignancies (PMID: 31091374). Mutations in PIK3CA lead to hyperactivation of the PI3K/AKT/mTOR signaling pathway, driving tumor progression and resistance to therapy. The p110δ and p110γ isoforms are predominantly expressed in leukocytes and are critical for immune cell function, making them key targets for hematological cancers and inflammatory diseases (PMID: 25049251, PMID: 30280635). While several PI3K inhibitors have been approved, their clinical utility is often constrained by significant on-target toxicities, such as hyperglycemia and rash for p110α inhibitors, and immune-mediated colitis or hepatotoxicity for p110δ/γ inhibitors (PMID: 28972030).

Other names

PI3K class IPhosphoinositide 3-kinase class Ip110-alphap110-deltap110-gammaPIK3CAPIK3CDPIK3CGPhosphatidylinositol 4,5-bisphosphate 3-kinase

Inhibition of the catalytic activity of Class I PI3K isoforms (p110α, p110δ, p110γ), preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby suppressing the downstream AKT/mTOR signaling pathway (PMID: 30447065).