Structural Insight into the Binding Mode of FXR and GPBAR1 Modulators

Handb Exp Pharmacol. 2019:256:111-136. doi: 10.1007/164_2019_234.

Abstract

In this chapter we provide an exhaustive overview of the binding modes of bile acid (BA) and non-BA ligands to the nuclear farnesoid X receptor (FXR) and the G-protein bile acid receptor 1 (GPBAR1). These two receptors play a key role in many diseases related to lipid and glucose disorders, thus representing promising pharmacological targets. We pay particular attention to the chemical and structural features of the ligand-receptor interaction, providing guidelines to achieve ligands endowed with selective or dual activity towards the receptor and paving the way to future drug design studies.

Keywords: Bile acids; FXR; GPBAR1; Homology modelling; Molecular docking; Molecular dynamics (MD); X-ray crystallography.

Publication types

  • Review

MeSH terms

  • Bile Acids and Salts / metabolism*
  • Drug Design
  • Humans
  • Ligands
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Bile Acids and Salts
  • GPBAR1 protein, human
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor