Phosphoinositide 3-kinase inhibitors (PI3K inhibitors) are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable. After PI3K inhibitors had been under investigation as anti-cancer drugs for several years, the first one to be approved for treatment in clinical practice was idelalisib in 2014. Several others followed, and even more are still under development (see below). There are different classes and isoforms of PI3Ks. Class 1 PI3Ks have a catalytic subunit known as p110, with four types (isoforms) – p110 alpha (PIK3CA), p110 beta (PIK3CB), p110 gamma (PIK3CG) and p110 delta (PIK3CD). All PI3K inhibitors that are currently approved inhibit one or more p110 isoforms of the class I PI3Ks. Inhibiting different p110 isoforms can have different effects, e.g. PTEN-negative tumors may be more sensitive to PIK3CB inhibitors. PI3K inhibitors are also under investigation as treatments for inflammatory respiratory disease, and are used to investigate the role of the PI3K pathway in aging.

Approved for treatment

Under clinical development

Late stage

In phase III clinical trials: In phase II clinical trials:

Early stage

In early stage clinical trials

Not in clinical trials