Phosphoinositide 3-kinase (PI3K)

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate the 3-hydroxyl position of phosphoinositides, principally converting phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) into phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3)[3][6]. They act as central signal transducers in cellular pathways downstream of a variety of cell-surface receptors, including receptor tyrosine kinases and G protein-coupled receptors[3][4]. PI3Ks play a crucial role in regulating cell growth, proliferation, survival, metabolism, migration, and immune cell function[1][5][8]. Dysfunction or aberrant activation of PI3K, particularly the class I isoforms (including p110α, β, δ, γ), is implicated in cancer, inflammatory disorders, and metabolic diseases[4][8]. The class I PI3Ks are heterodimers with catalytic p110 and regulatory subunits; p85 is typical for class IA and p101/p84 for class IB[4][3][6]. PI3K’s enzymatic reaction products (such as PIP3) serve as second messengers, recruiting and activating downstream proteins containing pleckstrin homology (PH) or similar domains, most notably Akt (protein kinase B)[1][5]. Many isoform-selective PI3K inhibitors have been developed as anticancer and anti-inflammatory therapeutics, especially for malignancies harboring activating mutations in PIK3CA (encoding p110α)[8]. Approved drugs include idelalisib, copanlisib, duvelisib, and alpelisib, with adverse effects largely resulting from on-target inhibition in normal tissues (notably metabolic and immune cells), leading to risks such as hyperglycemia and immunosuppression.

Other names

phosphatidylinositol 3-kinasePI 3-kinasePI3 kinasePI3Ksphosphoinositide-3-kinase

Inhibition of lipid kinase activity (preventing formation of PIP3), downstream blockade of Akt/PKB signaling, suppression of cell survival, proliferation, migration, and metabolism