targetsTarget

PI3K delta (PIK3CD)

The blood-cell version of the PI3K survival signal that keeps B cells alive. Idelalisib, duvelisib and copanlisib block it in chronic lymphocytic leukaemia and follicular lymphoma, at the price of immune-related colitis, liver inflammation and infections that have limited their use.

The delta isoform of PI3K is restricted to white blood cells and relays B-cell receptor signalling, so blocking it starves malignant B cells of a survival signal. Idelalisib was approved in 2014 for relapsed CLL with rituximab and for follicular lymphoma, duvelisib in 2018 and copanlisib in 2017, but autoimmune-type toxicities, opportunistic infections and unfavourable survival signals in confirmatory trials led to the withdrawal of the follicular lymphoma indications in 2022 and of copanlisib in 2023. BTK inhibitors and venetoclax have largely taken their place, and the class is a case study in the limits of accelerated approval.

PI3K delta (PIK3CD): what it is and how drugs act on it · animated generic schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · The blood-cell version of the PI3K survival signal that keeps B cells alive. Idelalisib, duvelisib and copanlisib block it in chronic lymphocytic leukaemia and follicular lymphoma, at the price of immune-related colitis, liver inflammation and infections that have limited their use.

1 · What it is
The blood-cell version of the PI3K survival signal that keeps B cells alive. Idelalisib, duvelisib and copanlisib block it in chronic lymphocytic leukaemia and follicular lymphoma, at the price of immune-related colitis, liver inflammation and infections that have limited their use.
2 · What goes wrong in cancer
Leukocyte-restricted class I PI3K catalytic subunit downstream of the B-cell receptor; isoform-selective inhibitors spare the ubiquitous alpha and beta isoforms.
3 · How drugs use it
No product in this corpus aims at PI3K delta (PIK3CD) yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.

Full dossier: hotspots, trials, resistance, assays, models, open questions →

External identifiers

PIK3CDHGNCEnsemblUniProtAlphaFold DBOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI Gene

Biology

Leukocyte-restricted class I PI3K catalytic subunit downstream of the B-cell receptor; isoform-selective inhibitors spare the ubiquitous alpha and beta isoforms.

Where it is found