Phosphoinositide 3-kinase catalytic subunit gamma (p110γ) (p110γ)

p110γ, encoded by the PIK3CG gene, is the catalytic subunit of the Class IB phosphoinositide 3-kinase (PI3Kγ) enzyme (NIH, 2026). Unlike Class IA PI3Ks which are typically activated by receptor tyrosine kinases, p110γ is primarily activated by G protein-coupled receptors (GPCRs) through interaction with Gβγ subunits (NIH, 2026). It is highly expressed in immune cells, where it regulates critical processes such as chemotaxis, cell migration, and inflammatory responses (NIH, 2026). In the context of oncology, p110γ is a major driver of immune suppression within the tumor microenvironment by promoting the recruitment and polarization of myeloid-derived suppressor cells and M2-type macrophages (NIH, 2021). Pharmacological inhibition of p110γ, using agents like eganelisib, is being explored to reprogram the tumor immune landscape and enhance the efficacy of immunotherapies (ClinicalTrials.gov, 2024). Additionally, its role in leukocyte recruitment makes it a therapeutic target for various inflammatory and autoimmune conditions such as rheumatoid arthritis and asthma (NIH, 2009).

Other names

PIK3CGp110-gammaPI3K-gammaPI3KγPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformPhosphoinositide 3-kinase catalytic subunit gamma

ATP-competitive inhibition of the p110γ catalytic subunit, which prevents the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby blocking downstream Akt/mTOR signaling and modulating immune cell trafficking and polarization.