Farnesoid X receptor (FXR): Structures and ligands

Longying Jiang; Huajun Zhang; Desheng Xiao; Hudie Wei; Yongheng Chen

doi:10.1016/j.csbj.2021.04.029

Farnesoid X receptor (FXR): Structures and ligands

Comput Struct Biotechnol J. 2021 Apr 20:19:2148-2159. doi: 10.1016/j.csbj.2021.04.029. eCollection 2021.

Authors

Longying Jiang^{1

2}, Huajun Zhang², Desheng Xiao¹, Hudie Wei^{1

2}, Yongheng Chen^{1

2}

Affiliations

¹ Department of Pathology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
² Department of Oncology, NHC Key Laboratory of Cancer Proteomics, Laboratory of Structural Biology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Abstract

Farnesoid X receptor (FXR) is a bile acid activated nuclear receptor (BAR) and is mainly expressed in the liver and intestine. Upon ligand binding, FXR regulates key genes involved in the metabolic process of bile acid synthesis, transport and reabsorption and is also involved in the metabolism of carbohydrates and lipids. Because of its important functions, FXR is considered as a promising drug target for the therapy of bile acid-related liver diseases. With the approval of obeticholic acid (OCA) as the first small molecule to target FXR, many other small molecules are being evaluated in clinical trials. This review summarizes the structures of FXR, especially its ligand binding domain, and the development of small molecules (including agonists and antagonists) targeting FXR.

Keywords: Agonists; Antagonists; Farnesoid X receptor; Ligand binding domain; Structure.

Publication types

Review