Identification of novel farnesoid X receptor modulators using a combined ligand- and structure-based virtual screening

Abstract

A combined ligand- and structure-based virtual screening has been applied to retrieve novel modulators of the farnesoid X receptor (FXR). Four distinct chemotypes exhibiting partial activation of FXR in a reporter gene assay could be identified. The analysis of the preliminary structure–activity relationships yielded a 3-amino-imidazo[1,2-a]pyridine derivative which showed a maximum relative FXR activation of about 14% with an EC₅₀ = 480 nM.