Phosphoinositide 3-kinase - Wikipedia
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.
A small-molecule PI3Kα activator for cardioprotection and ...
May 24, 2023 · Class IA PI3Ks signal downstream of tyrosine kinases, G protein-coupled receptors and small GTPases to regulate cell metabolism, growth, proliferation and migration.
Structural insights into isoform-specific RAS-PI3Kα ... - Nature
6 days ago · Mutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα ...
Loss of PI3Kα Mediates Protection From Myocardial …
Jun 15, 2023 · The chronic loss of phosphoinositide 3‐kinase alpha (PI3Kα) signaling is known to increase the susceptibility to myocardial infarction 8, 9 and pressure‐induced 10 heart failure. Surprisingly, PI3Kα‐dominant negative hearts (p110α‐DN) are resistant to IR injury.
PI3K inhibitors are finally coming of age
Jun 14, 2021 · Although progress has been hampered by issues such as poor drug tolerance and drug resistance, several PI3K inhibitors have now received regulatory approval — the PI3Kα isoform-selective...
The PI3K pathway in human disease - PMC - PubMed Central (PMC)
Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. We also discuss recent progress developing PI3K-targeted therapies for treatment of …
The role of PI3Kα isoform in cardioprotection - PMC
Oct 17, 2017 · PI3Kα expression and activation in cells and tissues. PI3Kα is expressed in a similar proportion in both mouse heart and human atrial tissue. Moreover, PI3Kα activity can be pharmacologically modulated in both tissues, as demonstrated using its canonical activator and specific inhibitor.
The present and future of PI3K inhibitors for cancer therapy
The first clinical PI3Kα-specific inhibitor, alpelisib, was developed with the aim of targeting the PI3K pathway (when activated by the p110α isoform), but limiting the emergence of toxicities attributed to inhibition of other isoforms of p110 25,70.
PI3K Driver Mutations: A Biophysical Membrane-Centric Perspective
PI3Kα, the key member of the PI3K lipid kinase family, is one of the most highly mutated proteins in cancer and an important drug target (40–47). PI3Kα is an obligate heterodimer, containing the regulatory p85α and the catalytic p110α subunits .
PI3K inhibitors: review and new strategies - PubMed
May 19, 2020 · Here we briefly review PI3Kα mutations, focus on PI3K drug repertoire and propose new, to-date unexplored PI3Kα therapeutic strategies. These include (1) an allosteric and orthosteric inhibitor combination and (2) taking advantage of …