PX-866, PI3-kinase inhibitor

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.

Activity summary

The mechanistic target of rapamycin known as mTOR plays an important role in cellular growth and metabolism. mTOR belongs to the phosphatidylinositol 3-kinase-related kinase family and weighs approximately 289 kDa. It operates mainly in two complexes mTORC1 and mTORC2 each differing in function and structure. PIK3CA another key component specifically acts as a catalytic subunit and is often associated with Class I PI3K. The gene expression of mTOR and PIK3CA occurs ubiquitously but they show higher activity in tissues experiencing rapid growth like muscle and liver. PRKACG or protein kinase A catalytic subunit gamma functions as an important signaling protein across many cell types.

Biological function summary

MTOR regulates the cell cycle cell growth and protein synthesis by integrating signals from nutrients and energy status. Within the cell mTORC1 and mTORC2 belong to separate biochemical complexes that are regulating a range of functions. PI3 kinase activity of PIK3CA facilitates the activation of mTORC1 by generating phosphatidylinositol-345-trisphosphate (PIP3) important for subsequent protein activation steps. PRKACG engages in signaling pathways promoting cellular responses through cyclic adenosine monophosphate (cAMP). Together these components orchestrate cellular metabolic demands with extracellular growth signals.

Pathways

These proteins participate prominently in the PI3K/AKT/mTOR signaling pathway critical for cellular proliferation and survival. This pathway includes a sequence beginning with PI3 kinase's conversion of phosphatidylinositol to PIP3 leading to AKT activation. The pathway concludes with mTOR activation further regulating ribosomal protein S6 kinase and eukaryotic initiation factor 4E-binding protein. Another related pathway is the cAMP signaling pathway where PRKACG contributes through protein kinase A-mediated activation mechanisms. These pathways are engaged with proteins like AKT as well as ribosomal proteins indicating intricate interdependencies.

Associated diseases and disorders

Dysregulation of the PI3K/AKT/mTOR signaling pathway often correlates with cancer particularly in mutations of PIK3CA which enhance PI3 kinase activity and promote unchecked cellular proliferation. Similarly mTOR malfunction has links with diabetes specifically through insulin resistance where mTORC1 affects glucose metabolism. PRKACG's abnormal activity also appears in certain cancers highlighting its role in different signaling cascades. Connections between mTOR PIK3CA and AKT highlight the complexity of cancer pathophysiology pointing to potential therapeutic targets within these pathways.