Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT.

ABSTRACT: AKT is the main protein kinase of the PI3K-AKT pathway, interacting with over one hundred protein partners to facilitate cellular processes that allow cancer cells to survive and proliferate. It is an attractive target due to its control over many cellular outputs. However, ATP-competitive and allosteric AKT inhibitors have performed poorly in clinical trials. AKT inhibitor interactions with AKT are multifaceted and influence the catalytic activity of AKT, its conformation, its ability to interact with binding partners, and its phosphorylation state. Therefore, a better understanding of how these inhibitors influence these parameters is needed, especially in a cellular context. Using a live-cell NanoBRET target engagement assay to query the binding of AKT inhibitors to all isoforms of AKT,

SUBMITTER: Harris JW 

PROVIDER: S-EPMC12281477 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature