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 ...

Jan 13, 2025 · The acquisition will expand Lilly's oncology pipeline with STX-478, the differentiated and potentially best-in-class, mutant-selective PI3Kα inhibitor currently in a Phase 1/2 clinical trial. STX-478 could potentially address 30-40% of people with hormone-positive breast cancer, building on Lilly's advancements against this disease

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.

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 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...

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.

Mar 26, 2021 · PI3Ks are important lipid kinases that produce phosphoinositides phosphorylated in position 3 of the inositol ring. There are three classes of PI3Ks: class I PI3Ks produce PIP3 at plasma membrane level.

Feb 23, 2012 · Phosphoinositide 3-kinases (PI3Ks) generate intracellular lipids that affect a range of cell biological phenomena. They phosphorylate the 3-OH group of inositol membrane lipids to modulate...