Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma and phosphatidylinositol 4,5-bisphosphate 3-kinase delta (PI3Kγ and PI3Kδ)

Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma (PI3Kγ) and phosphatidylinositol 4,5-bisphosphate 3-kinase delta (PI3Kδ) are members of the Class I phosphoinositide 3-kinase family of enzymes, which catalyze the phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2) to generate phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a key lipid signaling molecule[1][2][5][7]. PI3Kγ is encoded by the PIK3CG gene, primarily expressed in myeloid and other immune cells, and is regulated chiefly by G protein-coupled receptors (GPCRs)[1][2]. It mediates cell migration, chemotaxis, and activation in immune responses and inflammation. PI3Kδ, encoded by the PIK3CD gene, is selectively expressed in leukocytes and is involved in antigen receptor signaling in B cells and T cells, regulating proliferation, survival, and immune function[1][3][5]. Both isoforms are implicated in diseases characterized by immune dysregulation and cancer, have become validated targets for selective small molecule therapeutics, and play crucial roles in the physiological and pathological modulation of immune cell function. Therapeutic inhibition of these isoforms is associated with both efficacy (particularly in lymphoid tumors and inflammatory conditions) and immune-related adverse effects due to broad involvement in immune signaling pathways[5][7]

Other names

PI3K gamma (for PI3Kγ)PI3K delta (for PI3Kδ)Phosphoinositide 3-kinase gammaPhosphoinositide 3-kinase deltap110γ (for PI3Kγ)p110δ (for PI3Kδ)PIK3CG (gene encoding PI3Kγ)PIK3CD (gene encoding PI3Kδ)

Inhibition of PI3Kδ: blocks B-cell signaling, survival, and migration—useful in B-cell malignancies Inhibition of PI3Kγ: impairs innate immune cell (e.g., neutrophil, macrophage) migration and activation, reducing inflammation and tumor microenvironment-mediated immune suppression[5][7]