PI3K inhibitors
Oral kinase inhibitors of the PI3K-AKT pathway: alpelisib (PI3Kα) for PIK3CA-mutant breast cancer, idelalisib (PI3Kδ) for B-cell cancers.
What they are
Phosphoinositide 3-kinases (PI3K) relay signals from growth-factor and B-cell receptors to AKT and mTOR, promoting growth and survival. The isoform decides the use: PI3Kα (gene PIK3CA) is often mutated in hormone receptor-positive breast cancer; PI3Kδ is expressed mainly in leukocytes and supports malignant B cells.
Mechanism of action
They compete with ATP in the kinase site of the PI3K catalytic subunit, so PIP3 is not formed and AKT-mTOR signalling falls. Alpelisib is selective for PI3Kα; idelalisib for PI3Kδ, which also reduces B-cell receptor and chemokine (CXCR4, CXCR5) signalling and the homing of B cells to lymph nodes and marrow.
Target: Phosphoinositide 3-kinase catalytic subunits (PI3Kα, PI3Kδ)
Drugs in this class
- AlpelisibOral PI3Kα inhibitor used with fulvestrant in PIK3CA-mutant breast cancer, and for PIK3CA-related overgrowth…PI3Kα, catalytic subunit p110α of phosphoinositide 3-kinase
- IdelalisibOral PI3Kδ inhibitor for relapsed CLL with rituximab. Boxed warnings: liver damage, severe diarrhoea or colitis…PI3Kδ, catalytic subunit p110δ of phosphoinositide 3-kinase (leukocytes)
Others in the class
- copanlisib
- duvelisib
- inavolisib
Test yourself
Think of the answer, then tap the question to see it.
Why does alpelisib raise blood glucose?
Because PI3Kα is part of the insulin signalling pathway in liver, muscle and fat.
Which PI3K isoform does idelalisib target, and in which cells is it expressed?
PI3Kδ, expressed mainly in leukocytes, including normal and malignant B cells.
Which three boxed toxicities of idelalisib can you name?
Any three of: hepatotoxicity, severe diarrhoea or colitis, pneumonitis, serious infections, intestinal perforation.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Alpelisib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Idelalisib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.