Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta (PI3K delta) (PI3K delta)

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta (PI3K delta) is a member of the Class IA phosphoinositide 3-kinase family, primarily expressed in hematopoietic cells such as B cells, T cells, and myeloid cells [1.2.1, 1.4.1]. It functions as a lipid kinase that phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) at the plasma membrane, a critical second messenger that recruits PH-domain-containing proteins like AKT and PDK1 [1.3.2, 1.4.2]. This signaling cascade is vital for the development, activation, and survival of lymphocytes and other immune cells [1.2.2, 1.4.2]. Overactivation of PI3K delta, often through gain-of-function mutations in the PIK3CD gene, leads to Activated PI3K Delta Syndrome (APDS), while its dysregulation is a hallmark of various B-cell malignancies [1.2.3, 1.4.3]. Selective inhibitors of PI3K delta have been developed to treat chronic lymphocytic leukemia, follicular lymphoma, and APDS by blocking the aberrant survival signals in these cells [1.1.5, 1.4.3]. However, therapeutic use is often limited by immune-mediated toxicities, including colitis and pneumonitis, which result from the disruption of immune homeostasis [1.1.1, 1.1.2].

Other names

PIK3CDp110 deltap110δPhosphoinositide 3-kinase deltaPtdIns-3-kinase subunit deltaIMD14APDS

Selective inhibition of the p110δ catalytic subunit of Class IA PI3K, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) and subsequent activation of the AKT/mTOR signaling pathway in leukocytes [1.3.2, 1.4.1, 1.4.2].