Phosphoinositide 3-kinase Class I (PI3K Class I) (PI3K Class I)

Class I phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases consisting of four catalytic isoforms: p110α, p110β, p110γ, and p110δ [2, 7]. These enzymes play a central role in cellular signaling by phosphorylating phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3), which activates downstream effectors like AKT and mTOR [8, 12]. This pathway is critical for regulating cell growth, proliferation, survival, metabolism, and immune cell function [2, 13]. Dysregulation of PI3K signaling, often through mutations in the PIK3CA gene or loss of the PTEN tumor suppressor, is a hallmark of many human cancers and inflammatory conditions [4, 17]. Therapeutic strategies include pan-PI3K inhibitors that target all four isoforms and isoform-selective inhibitors designed to maximize efficacy while minimizing off-target toxicities [5, 6]. While effective in treating various malignancies, PI3K inhibition is associated with specific safety concerns such as hyperglycemia, hepatotoxicity, and immune-related adverse events [10, 14].

Other names

PI3K alpha/beta/gamma/deltaClass I PI3Kp110 alpha/beta/gamma/deltaPhosphatidylinositol 3-kinase Class I

ATP-competitive inhibition of Class I PI3K catalytic subunits (p110α, p110β, p110γ, p110δ), preventing the conversion of PIP2 to PIP3 and inhibiting the downstream PI3K/AKT/mTOR signaling pathway [8, 13].