Phosphoinositide 3-kinase and mechanistic target of rapamycin kinase (PI3K and mTOR)

Phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin kinase (mTOR) are central components of the intracellular PI3K/AKT/mTOR signaling pathway, which is essential for regulating cell growth, proliferation, survival, metabolism, and apoptosis. PI3K is a lipid kinase family that phosphorylates phosphatidylinositols at the 3' position to generate PIP3, leading to downstream activation of AKT and, subsequently, mTOR. mTOR is a serine/threonine kinase and a core component of two distinct complexes, mTORC1 and mTORC2, each controlling different aspects of cellular growth and metabolism. Both PI3K and mTOR are frequently dysregulated in cancer and other diseases, making them major drug targets in oncology and beyond. Therapeutic strategies include specific inhibitors of PI3K or mTOR, as well as dual inhibitors that target both kinases simultaneously, aiming to suppress aberrant cell proliferation and survival signals in tumors

Other names

PI3Kphosphatidylinositol 3-kinasephosphatidylinositol-4,5-bisphosphate 3-kinasemTORmammalian target of rapamycinFK506-binding protein 12-rapamycin associated protein 1 (FRAP1)

PI3K inhibitors: block PI3K catalytic activity to reduce production of PIP3, inhibiting activation of downstream AKT and mTOR pathways. mTOR inhibitors: inhibit the mTOR kinase, blocking mTORC1 (and in some cases mTORC2) activity, suppressing cell growth, proliferation, and metabolism. Dual PI3K/mTOR inhibitors: simultaneously target both kinases to suppress pathway activity more completely and potentially overcome resistance.