Comprehensive assessment of NR ligand polypharmacology by a multiplex reporter NR assay.

ABSTRACT: Nuclear receptors (NR) are ligand-modulated transcription factors that regulate multiple cell functions and thus represent excellent drug targets. However, due to a considerable NR structural homology, NR ligands often interact with multiple receptors. Here, we describe a multiplex reporter assay (the FACTORIAL NR) that enables parallel assessment of NR ligand activity across all 48 human NRs. The assay comprises one-hybrid GAL4-NR reporter modules transiently transfected into test cells. To evaluate the reporter activity, we assessed their RNA transcripts. We used a homogeneous RNA detection approach that afforded equal detection efficacy and permitted the multiplex detection in a single-well format. For validation, we examined a panel of selective NR ligands and polypharmacological agoni

SUBMITTER: Medvedev A 

PROVIDER: S-EPMC8873415 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature