Phosphoinositide 3-kinase class II (PI3K Class II) (Class II PI3K)

Class II Phosphoinositide 3-kinases (PI3Ks) are a distinct group of lipid kinases comprising three isoforms: PI3K-C2α, PI3K-C2β, and PI3K-C2γ (UniProt). Unlike Class I PI3Ks, which primarily generate PI(3,4,5)P3 at the plasma membrane to drive AKT signaling, Class II PI3Ks mainly produce PI(3)P and PI(3,4)P2, which are critical for membrane trafficking, endocytosis, and intracellular compartmentalized signaling (PubMed: 29453281). These enzymes play vital roles in diverse physiological processes, including angiogenesis, platelet function, and glucose homeostasis (PubMed: 30635424). Dysregulation of Class II PI3Ks is implicated in various pathologies, such as cancer progression, metabolic disorders, and thrombosis (PubMed: 28258213). While historically less studied than Class I, Class II PI3Ks are emerging as potential therapeutic targets, particularly in oncology and metabolic disease. However, the development of isoform-specific inhibitors remains a significant challenge due to the structural similarities within the kinase family and the potential for metabolic or vascular side effects (PubMed: 31431619).

Other names

PI3K-C2PIK3C2Phosphatidylinositol 3-kinase class 2PI3K-C2 alpha (PIK3C2A)PI3K-C2 beta (PIK3C2B)PI3K-C2 gamma (PIK3C2G)

Inhibition of the catalytic domain of Class II PI3K isoforms to prevent the phosphorylation of phosphatidylinositol (PI) and phosphatidylinositol 4-phosphate (PI4P), thereby reducing the production of PI(3)P and PI(3,4)P2 and disrupting endosomal trafficking and downstream signaling (PubMed: 29453281).