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.
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.
Structural insights into isoform-specific RAS-PI3Kα ... - Nature
Jan 9, 2025 · 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 ...
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...
Activating the kinase protein PI3Kα revealed as a potential …
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.
PI3K inhibitors: review and new strategies - RSC Publishing
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 allosteric rescue mutations to guide drug discovery.
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.
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.
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 …
A small molecule PI3Kα activator for cardioprotection and ...
Jun 6, 2023 · 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 ...
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