Phosphoinositide 3-kinase class I (PI3K (class I))

Phosphoinositide 3-kinase class I (class I PI3K) refers to a family of heterodimeric lipid kinases that phosphorylate phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P₂) to generate phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P₃), a key second messenger in signal transduction pathways[1][2][5][6]. Class I PI3Ks are divided into class IA (p110α, p110β, p110δ—encoded by PIK3CA, PIK3CB, PIK3CD) and class IB (p110γ—encoded by PIK3CG); each forms a heterodimer with a regulatory subunit (such as p85 or p101/p84)[1][4][7]. These kinases are activated downstream of receptor tyrosine kinases, G protein-coupled receptors, or small GTPases, leading to activation of AKT and mTOR and subsequent regulation of vital cellular processes such as growth, metabolism, proliferation, survival, motility, and immune function[2][4][5][6]. Class I PI3Ks are frequently mutated or dysregulated in various cancers (notably PIK3CA in breast, colon, and other cancers), and have emerged as major therapeutic targets, with multiple specific inhibitors developed or approved for use in oncology and immune-related disorders[2][4][5][6]. Prominent safety concerns with targeted PI3K inhibitors include effects on glucose metabolism, immune suppression, and gastrointestinal, hepatic, or cutaneous toxicities[2][4][5].

Other names

Class I PI3KClass I phosphoinositide 3-kinasePI3Kα (PIK3CA)PI3Kβ (PIK3CB)PI3Kγ (PIK3CG)PI3Kδ (PIK3CD)p110αp110βp110γp110δ

Inhibition of the p110 catalytic activity (either pan-PI3K or isoform-specific inhibition) - Blockade of downstream PI3K-AKT-mTOR pathway signaling to suppress cell growth, proliferation, and survival