Pharmacophore modeling and virtual screening studies for discovery of novel farnesoid X receptor (FXR) agonists.

ABSTRACT: Farnesoid X receptor (FXR) agonists would be considered as an important therapeutic strategy for several chronic liver and metabolic diseases. Here we have employed an integrated virtual screening by combining ligand-based pharmacophore mapping and molecular docking to identify novel nonsteroidal FXR agonists. Eighteen compounds were selected for in vitro FXR agonistic activity assay, and results showed five compounds exhibiting promising FXR agonistic activity. Among these compounds, compounds F4 and F17 were the most remarkable in vitro activity by using homogeneous time resolved fluorescence (HTRF) assay and the full-length FXR reporter gene assay in HepG2 cells. Real-time PCR assay was performed to measure the expression of FXR target genes. Compounds F4 and F17 increased

SUBMITTER: Zhao S 

PROVIDER: S-EPMC8693749 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature