ATC Group: L01EM Phosphatidylinositol-3-kinase (Pi3K) inhibitors

Alpelisib is an α-specific class I phosphatidylinositol3kinase (PI3Kα) inhibitor. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and AKT-signalling, cellular transformation and the generation of tumours in in vitro and in vivo models.

Copanlisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-α and PI3K-δ isoforms expressed in malignant B cells. Copanlisib has been shown to induce tumor cell death by apoptosis and inhibition of proliferation of primary malignant B cell lines.

Duvelisib is a dual inhibitor of phosphatidylinositol 3-kinase p110δ (PI3K-δ) and PI3K-γ. PI3K-δ inhibition directly reduces proliferation and survival of malignant B-cell lines and primary CLL tumour cells, while PI3K-γ inhibition reduces the activity of CD4+ T cells and macrophages in the tumor microenvironment to support the malignant B cells.

Idelalisib inhibits phosphatidylinositol 3-kinase p110δ (PI3Kδ), which is hyperactive in B-cell malignancies and is central to multiple signalling pathways that drive proliferation, survival, homing, and retention of malignant cells in lymphoid tissues and bone marrow. Idelalisib induces apoptosis and inhibits proliferation in cell lines derived from malignant B-cells and in primary tumour cells.