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Phosphatidylinositol 4,5-bisphosphate 3-kinase delta (PI3Kδ)
- Target
- PI3Kδ
- Molecular classification
- Lipid Kinase, Class IA PI3K, Enzyme
01
Overview
Phosphatidylinositol 4,5-bisphosphate 3‑kinase delta is a class IA lipid kinase crucial for generating second messengers that regulate survival/proliferation signals predominantly within leukocytes. Its precise regulation underpins normal immunity while dysregulation causes immunodeficiencies like APDS or contributes to cancer pathogenesis. Selective pharmacological inhibition offers targeted therapy options but requires careful balancing between efficacy and safety.
- Other names
- PIK3CDp110δ
02
Mechanism of action
Inhibition of PI3Kδ catalytic activity, preventing the conversion of PtdIns(4,5)P₂ to PtdIns(3,4,5)P₃ and subsequent activation of downstream signaling pathways like AKT/mTOR.
03
Biological functions
Regulation of cell growth and survivalControl of proliferation and differentiationModulation of motility and intracellular traffickingB-cell receptor signalingT-cell receptor signalingSignal transductionImmune response
04
Disease associations
ImmunodeficiencyActivated Phosphoinositide 3-Kinase Delta Syndrome (APDS)Hematologic cancers
05
Safety considerations
ColitisNeutropeniaHepatotoxicityImmune suppression (with less selective inhibitors)
06
Interacting drugs
Leniolisib
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