Phosphoinositide 3-kinase gamma catalytic subunit (PI3Kγ)

Phosphoinositide 3-kinase gamma catalytic subunit (PI3Kγ, encoded by the PIK3CG gene) is the enzymatic subunit of the Class IB PI3Kγ complex, which is a lipid kinase predominantly expressed in leukocytes[1][4][7]. PI3Kγ catalyzes the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3), a key mediator in cellular signaling pathways regulating immune cell migration, chemotaxis, inflammatory responses, and cellular metabolic processes[3][4][7]. The enzyme is activated downstream of G protein-coupled receptors, via association with one of two regulatory subunits (p101 or p84), and is a critical regulator of immune cell function and inflammatory signaling[2][7]. Dysregulation or overactivation of PI3Kγ is implicated in numerous pathologies, including cancer (especially in the tumor microenvironment), cardiovascular disease, and a broad range of inflammatory and respiratory disorders[4][7][6][1]. Selective inhibition of PI3Kγ is a promising therapeutic strategy for conditions with pathologic myeloid immune cell activity, such as cancer and chronic inflammatory diseases[7][4][1]. Note: Only Eganelisib is a selective, clinical PI3Kγ inhibitor[7][4][1].

Other names

PI3K-gammaPI3Kγp110γphosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gammaPIK3CG

Competitive inhibition of ATP binding site (for most small molecule inhibitors). Suppression of PI3Kγ kinase activity, blocking the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), inhibiting downstream AKT/mTOR signaling[3][1][6]. Immunomodulation, particularly reducing myeloid cell-driven immune suppression in the tumor microenvironment[7].