Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) (PIK3CD)

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), also known as p110δ, is a class IA PI3K enzyme primarily expressed in leukocytes [1, 6]. It plays a critical role in the signaling pathways of B-cell and T-cell receptors, regulating immune cell proliferation, differentiation, and survival [2, 5]. Dysregulation of PIK3CD is linked to various pathologies, including hematologic malignancies like chronic lymphocytic leukemia (CLL) and follicular lymphoma, as well as primary immunodeficiencies such as Activated PI3K-delta Syndrome (APDS) [2, 11]. Therapeutic targeting of PIK3CD involves small-molecule inhibitors that block its catalytic activity, thereby inhibiting the conversion of PIP2 to PIP3 and dampening downstream AKT/mTOR signaling [1, 12]. While effective in treating certain cancers and immune disorders, these inhibitors are associated with significant safety concerns, including immune-mediated toxicities like colitis and an increased risk of opportunistic infections [3, 11].

Other names

p110-deltaPI3K-deltaP110DELTAAPDSIMD14IMD14AIMD14BROCHISp110D

Selective or pan-inhibition of the p110δ catalytic subunit, which prevents the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) [1, 12]. This blockade disrupts the recruitment of PH-domain containing proteins like AKT and PDK1 to the plasma membrane, thereby inhibiting downstream signaling pathways (AKT/mTOR) essential for immune cell growth, survival, and proliferation [5, 10].