Identification of Small Molecule Ligand Binding Sites On and In the ARNT PAS-B Domain.

ABSTRACT: Transcription factors are generally challenging to target with small molecule inhibitors due to their structural plasticity and lack of catalytic sites. Notable exceptions include several naturally ligand-regulated transcription factors, including our prior work with the heterodimeric HIF-2 transcription factor which showed that small molecule binding within an internal pocket of the HIF-2α PAS-B domain can disrupt its interactions with its dimerization partner, ARNT. Here, we explore the feasibility of similarly targeting small molecules to the analogous ARNT PAS-B domain itself, potentially opening a promising route to simultaneously modulate several ARNT-mediated signaling pathways. Using solution NMR screening of an in-house fragment library, we previously identified several compounds

SUBMITTER: Xu X 

PROVIDER: S-EPMC10635134 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature