Class I phosphoinositide 3-kinase (Class I PI3K)

Class I phosphoinositide 3-kinases (PI3Ks) are a family of heterodimeric lipid kinases that catalyze the phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P₂) to generate phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P₃), a key second messenger that regulates diverse cellular processes including proliferation, survival, metabolism, and immune cell function[1][2][3][4][5][7]. This family consists of catalytic isoforms (p110α, p110β, p110δ for class IA; p110γ for class IB) and is regulated via interaction with adapter proteins (e.g., p85 for IA, p101 for IB). Class I PI3Ks are activated by receptor tyrosine kinases or G protein–coupled receptors, depending on the isoform[1][4]. Aberrant activation of PI3K signaling—through mutation, amplification, or loss of the antagonist PTEN—is common in cancers and inflammatory diseases, making the pathway a major therapeutic target. PI3K inhibitors are approved or in development for cancer and immunological disorders, but clinical use is limited by on-target side effects, including metabolic disturbances and immune suppression[5].

Other names

PI3K class IClass I PI3K catalytic subunitPhosphatidylinositol 3-kinase class IPI3Kα (for p110α)PI3Kβ (for p110β)PI3Kδ (for p110δ)PI3Kγ (for p110γ)

Inhibition of PI3K enzymatic activity, preventing generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and downstream signaling through Akt and other effector pathways[1][3][4][5]. Isoform-selective inhibition (e.g. PI3Kα, PI3Kδ) to exploit tumor-type or disease-selective vulnerabilities[5].