Phosphoinositide 3-kinase (PI3K)

Phosphoinositide 3-kinase (PI3K) refers to a family of intracellular lipid kinases that phosphorylate the 3-position hydroxyl group of the inositol ring of phosphoinositides. The most common substrate is phosphatidylinositol-4,5-bisphosphate (PIP2), yielding phosphatidylinositol-3,4,5-trisphosphate (PIP3). PI3Ks are divided into three classes (I, II, III) based on structure and substrate specificity; class I is the best described and most relevant to human disease, with four isoforms (p110α, β, γ, δ). PI3K signaling is crucial for controlling cell survival, growth, proliferation, metabolism, and motility, and it plays a major role in immune cell function. Dysregulation of PI3K, often through genetic mutation or overactivation, contributes to oncogenesis and is a common driver in several cancers; the pathway is also implicated in inflammation and immune disorders. Several PI3K inhibitors are approved or in development for cancer and immune diseases, but on-target toxicities present therapeutic challenges.

Other names

Phosphatidylinositol 3-kinasePhosphoinositide 3-kinasePI3KPI 3-kinasePhosphatidylinositol-4,5-bisphosphate 3-kinase

Inhibition of the kinase activity, blocking phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3), which reduces activation of the downstream AKT/mTOR pathway Immunomodulation (e.g., modulation of B cell or T cell signaling in inflammatory/autoimmune diseases)