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# PI3K inhibitors

Oral kinase inhibitors of the PI3K-AKT pathway: alpelisib (PI3Kα) for PIK3CA-mutant breast cancer, idelalisib (PI3Kδ) for B-cell cancers.

Updated Nov 1, 2026

## 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)

## Key points

- Alpelisib: hyperglycaemia is the signature effect (PI3Kα also carries insulin signalling); also rash and diarrhoea.
- Idelalisib: boxed warnings for hepatotoxicity, severe diarrhoea or colitis, pneumonitis, infections and intestinal perforation.
- Alpelisib is given with fulvestrant in PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer.
- Both are metabolised by CYP3A; idelalisib also inhibits CYP3A and raises levels of its substrates.

## Drugs in this class

- [**Alpelisib** Oral PI3Kα inhibitor used with fulvestrant in PIK3CA-mutant breast cancer, and for PIK3CA-related overgrowth… PI3Kα, catalytic subunit p110α of phosphoinositide 3-kinase](https://durgical.com/en/pharmacology/alpelisib/)
- [**Idelalisib** Oral PI3Kδ inhibitor for relapsed CLL with rituximab. Boxed warnings: liver damage, severe diarrhoea or colitis… PI3Kδ, catalytic subunit p110δ of phosphoinositide 3-kinase (leukocytes)](https://durgical.com/en/pharmacology/idelalisib/)

## 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.

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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](https://medlineplus.gov/druginfo/meds/a619036.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Idelalisib: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a614040.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01EM) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/pi3k-inhibitors/