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.

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.

Here we report on the discovery of UCL-TRO-1938 (further referred to as 1938), a small molecule activator of the PI3Kα isoform, a critical effector of growth factor signalling. 1938 allosterically activates PI3Kα through a unique mechanism, by enhancing multiple steps of the PI3Kα catalytic cycle, and causes both local and global ...

May 24, 2023 · Research into activators that can fix disease-linked molecular machines is underexplored. The lipid kinase protein phosphoinositide 3-kinase alpha (PI3Kα) is a key molecular machine controlling the activities of our cells.

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.

PIK3CA, which encodes the p110α catalytic subunit of PI 3-kinase alpha (PI3Kα), is one of the most frequently genetically-activated kinases in solid tumors.

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 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.

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...

Dec 4, 2024 · Using FRET and biolayer interferometry assays, we show that a class of ATP-site directed inhibitors represented by GSK2126458 block the growth factor activated PI3Kα WT membrane interaction, an activity dependent on the ligand forming specific ATP-site interactions.