Phosphatidylinositol 4,5-bisphosphate 3-kinase alpha (PI3Kα)

Phosphatidylinositol 4,5-bisphosphate 3-kinase alpha, commonly abbreviated as **PI3Kα**, is a catalytic subunit of class I phosphoinositide 3-kinases—a family of lipid kinases that phosphorylate the 3′-OH group of the inositol ring of phosphoinositides, generating phosphatidylinositol 3,4,5-trisphosphate[1][3]. PI3Kα plays a critical role in cellular signaling pathways that control proliferation, survival, metabolism, and migration[1][3][4]. The enzyme is a heterodimer composed of a p110α catalytic subunit (PIK3CA gene) and a regulatory subunit (p85 type), and is predominantly activated downstream of receptor tyrosine kinases[3]. Aberrant activation, often through **PIK3CA mutations**, is strongly implicated in a variety of cancers and other diseases[3][4]. Multiple selective inhibitors have been developed and approved for clinical use, primarily in oncology[4]. PI3Kα's involvement in diverse signaling cascades and its role as a driver of tumorigenesis make it a major therapeutic target, with inhibitors currently in clinical and preclinical development[4].

Other names

Phosphoinositide 3-kinase alphaPI3K alphaPI3Kαp110αClass I PI3K alpha isoformPIK3CA (gene symbol)

Small-molecule inhibitors block the kinase activity, preventing phosphorylation of phosphatidylinositol substrates and downstream activation of AKT and other effectors[4]. Allosteric inhibition by binding outside the ATP site (varies by inhibitor).