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

Class I phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinases that function as critical mediators in the PI3K/AKT/mTOR signaling pathway, which regulates fundamental cellular processes including growth, proliferation, survival, and metabolism (UniProt, 2024). This class is subdivided into four isoforms—alpha, beta, gamma, and delta—each with distinct expression patterns and physiological roles; for instance, alpha and beta are ubiquitously expressed, while gamma and delta are primarily found in hematopoietic cells (PubMed, 2023). Dysregulation of Class I PI3K signaling, frequently via PIK3CA mutations or PTEN tumor suppressor loss, is one of the most common drivers in human cancers, including breast, lung, and colorectal malignancies (NIH, 2023). Therapeutic targeting of these isoforms has led to the development of both pan-PI3K and isoform-specific inhibitors, such as alpelisib for PIK3CA-mutated breast cancer and idelalisib for B-cell malignancies (FDA, 2024). Despite their clinical utility, these drugs are associated with significant side effects, most notably hyperglycemia due to the alpha isoform's role in insulin signaling and immune-related toxicities linked to the delta isoform (StatPearls, 2024).

Other names

Phosphoinositide 3-kinasePI 3-kinasePI3-kinaseClass I PI3KsPhosphatidylinositol-4,5-bisphosphate 3-kinase

Inhibition of the catalytic activity of Class I PI3K isoforms, preventing the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), which subsequently inhibits the downstream AKT/mTOR signaling pathway (PubMed, 2023).