Phosphoinositide 3-kinase class I isoforms (PI3K class I) (PI3K class I)

Class I phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that play a pivotal role in the PI3K/AKT/mTOR signaling pathway, which is essential for regulating cell growth, proliferation, survival, and metabolism (UniProt: P42336, P42338). This family consists of four catalytic isoforms—p110α, p110β, p110γ, and p110δ—that are activated by various cell surface receptors to produce the second messenger PIP3 (PMID: 30635554). While p110α and p110β are ubiquitously expressed, p110γ and p110δ are primarily found in leukocytes, contributing to immune cell function and inflammation (PMID: 29735927). Dysregulation of these isoforms, frequently through PIK3CA mutations or PTEN loss, is a common driver in many human cancers, including breast, lung, and hematologic malignancies. Pan-class I PI3K inhibitors are therapeutic agents designed to inhibit all four isoforms simultaneously to achieve maximum suppression of the signaling pathway. However, the broad inhibition of these isoforms often leads to significant clinical challenges, including off-target toxicities such as hyperglycemia, gastrointestinal issues, and immune-related adverse events (PMID: 29735927).

Other names

PI3-kinase class IPhosphatidylinositol 3-kinase class Ip110 catalytic subunitsClass I PI3KsPan-PI3K

Pan-class I PI3K inhibitors act as ATP-competitive inhibitors that bind to the catalytic pocket of all four p110 isoforms (alpha, beta, gamma, and delta), thereby blocking the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and subsequent downstream signaling through the AKT/mTOR pathway (PMID: 29735927).