法尼醇X受体（FXR）和G蛋白偶联胆汁酸受体1（GPBAR1）调节剂结合模式的结构洞察

Structural Insight into the Binding Mode of FXR and GPBAR1 Modulators.

作者信息

Di Leva Francesco Saverio, Di Marino Daniele, Limongelli Vittorio

机构信息

Department of Pharmacy, University of Naples "Federico II", Naples, Italy.

Faculty of Biomedical Sciences, Institute of Computational Science, Center for Computational Medicine in Cardiology, Università della Svizzera italiana (USI), Lugano, Switzerland.

出版信息

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

DOI:10.1007/164_2019_234

PMID:31161298

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.

摘要

在本章中，我们详尽概述了胆汁酸（BA）和非BA配体与核法尼醇X受体（FXR）以及G蛋白胆汁酸受体1（GPBAR1）的结合模式。这两种受体在许多与脂质和葡萄糖紊乱相关的疾病中起着关键作用，因此是很有前景的药理学靶点。我们特别关注配体-受体相互作用的化学和结构特征，为获得对受体具有选择性或双重活性的配体提供指导，并为未来的药物设计研究铺平道路。