Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit (PI3K catalytic subunit) (PI3K catalytic subunit)

Phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) catalytic subunits, specifically the Class I p110 isoforms (alpha, beta, delta, and gamma), are essential enzymes that regulate a wide array of cellular functions [1][3]. They function by phosphorylating the 3-position of the inositol ring of PIP2 to produce PIP3, which serves as a docking site for signaling proteins containing PH domains, most notably AKT [1][2]. This activation triggers downstream pathways that promote cell survival, growth, and metabolic regulation [3]. In many human cancers, the PIK3CA gene (encoding the p110 alpha subunit) is frequently mutated or amplified, leading to constitutive pathway activation [3][5]. The delta and gamma isoforms are primarily expressed in leukocytes and are involved in immune cell signaling and inflammatory responses [1][4]. Therapeutic targeting of these subunits with small-molecule inhibitors has led to the approval of several drugs for breast cancer, lymphomas, and leukemias [4][5]. However, challenges such as off-target metabolic effects like hyperglycemia and immune-related toxicities remain significant hurdles in clinical management [5]. Isoform-specific inhibitors aim to improve the therapeutic window by targeting only the relevant subunit involved in the disease pathology [3]. Monitoring biomarkers such as PIK3CA mutation status is now standard practice for patient selection in certain indications [4]. Overall, these catalytic subunits represent a cornerstone of modern targeted oncology and immunology [3][5]. References: [1] UniProt (2023). "Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit series (P42336, P42338, O00329, P48736)." [2] NCBI Gene (2023). "PIK3CA, PIK3CB, PIK3CD, PIK3CG Phosphoinositide-3-kinase catalytic subunits." [3] Fruman, D. A., et al. (2017). "The PI3K Pathway in Human Disease." Cell, 170(4), 605-635. [4] FDA (2023). "Prescribing Information: Piqray (alpelisib), Zydelig (idelalisib), Copiktra (duvelisib)." [5] StatPearls (2023). "Phosphoinositide 3-Kinase (PI3K) Inhibitors."

Other names

p110PI3K p110 subunitPhosphoinositide-3-kinase catalytic subunitPIK3CPI3-kinase catalytic subunit

Inhibition of the ATP-binding site of the p110 catalytic subunit, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby suppressing the AKT/mTOR signaling pathway.