Modulation of the 14-3-3σ/C-RAF "auto"inhibited complex by molecular glues.

ABSTRACT: Molecular glues, compounds that bind cooperatively at protein-protein interfaces are revolutionizing chemical biology and drug discovery, allowing the modulation of traditional "undruggable" targets. Here, we focus on the native protein-protein interaction (PPI) of C-RAF, a key component of the MAPK signaling pathway, with the scaffolding protein 14-3-3. Although extensive drug discovery efforts have focused on the MAPK pathway, its central role in oncology and developmental disorders (RASopathies), still requires alternative approaches, moving beyond direct kinase inhibition. Indeed, stabilization of native PPIs is a relatively unexplored territory in this pathway. The function of C-RAF is regulated on multiple levels including dimerization, phosphorylation and complex formation with the

SUBMITTER: Konstantinidou M 

PROVIDER: S-EPMC12324506 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature