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Phosphatidylinositol 3-kinase delta (specifically, the catalytic subunit; also referred to by gene name PIK3CD) (PI3Kδ)
- Target
- PI3Kδ
- Molecular classification
- Enzyme, Lipid kinase, Class I phosphoinositide 3-kinase (class IA, catalytic subunit)
01
Overview
Phosphatidylinositol 3-kinase delta is a lipid kinase that catalyzes the phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) to generate phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3), an essential second messenger activating downstream proteins such as Akt. This enzyme is predominantly expressed in leukocytes and is a key regulator of immune cell signaling. Dysregulation or inhibition of PI3Kδ affects immune cell development, differentiation, and function, making it a critical drug target for the treatment of hematologic malignancies, autoimmune diseases, and disorders involving immune dysregulation. Several drugs target PI3Kδ for immunosuppressive or anti-cancer therapy, but their use is associated with notable safety risks due to their effects on immune cell function
- Other names
- PI3Kδp110δPhosphoinositide 3-kinase deltaPIK3CD
02
Mechanism of action
ATP-competitive inhibition of the kinase activity (thereby blocking formation of second messenger phosphatidylinositol (3,4,5)-trisphosphate, PI(3,4,5)P3) Reduces PI3Kδ-mediated signal transduction providing immunosuppression or anti-proliferative effects
03
Biological functions
Signal transductionImmune response (especially T cell, B cell, mast cell, and neutrophil function)Cell proliferationCell survivalMediator of inflammatory response
04
Disease associations
Cancer (especially hematological malignancies)InflammationAutoimmune diseaseTransplant rejection (immunological)Asthma
05
Safety considerations
Immune suppression (increased risk of infection—including pneumonia, colitis)HepatotoxicityDiarrheaIncreased risk of other immune-related adverse events
06
Interacting drugs
Idelalisib (approved for certain leukemias and lymphomas)
1 more in the full profile.
07
Biomarkers
PIK3CD mutations or expression (for patient stratification in immunodeficiencies and lymphoid malignancies)Downstream Akt/PKB phosphorylation (as pharmacodynamic biomarker for pathway inhibition)
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