Rapid, potent, and persistent covalent chemical probes to deconvolute PI3Kα signaling.

ABSTRACT: Chemical probes have gained importance in the elucidation of signal transduction in biology. Insufficient selectivity and potency, lack of cellular activity and inappropriate use of chemical probes has major consequences on interpretation of biological results. The catalytic subunit of phosphoinositide 3-kinase α (PI3Kα) is one of the most frequently mutated genes in cancer, but fast-acting, high-quality probes to define PI3Kα's specific function to clearly separate it from other class I PI3K isoforms, are not available. Here, we present a series of novel covalent PI3Kα-targeting probes with optimized intracellular target access and kinetic parameters. On-target TR-FRET and off-target assays provided relevant kinetic parameters (k _chem, k _inact and K<

SUBMITTER: Bissegger L 

PROVIDER: S-EPMC11575505 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature