This document summarizes a research article about using steroidal scaffolds as ligands for the FXR and GPBAR1 nuclear receptors. The article discusses how bile acids function as signaling molecules through these receptors and how modulating these receptors could help treat diseases like dyslipidemia, cholestasis, nonalcoholic steatohepatitis, type 2 diabetes, and inflammation. It describes how natural compounds and medicinal chemistry have been used to develop promising drug candidates that selectively or dually modulate FXR and GPBAR1.

1. Future Medicinal Chemistry 2015 Jul;7(9):1109-1135.
STEROIDAL SCAFFOLDS AS FXR AND GPBAR1 LIGANDS: FROM CHEMISTRY TO
THERAPEUTICAL APPLICATION.
Sepe V1, Distrutti E2, Limongelli V1,3, Fiorucci S4, Zampella A1.
1Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
2Hospital S. Maria della Misericordia, Perugia, Italy.
3Institute of Computational Science, Faculty of Informatics, Università della Svizzera Italiana (USI), Lugano,
Switzerland.
4Department of Experimental & Clinical Medicine, University of Perugia, Perugia, Italy.
Abstract
Bile acids (BAs) are experiencing a new life. Next to their ancestral roles in lipid digestion and solubilization,
BAs are today recognized signaling molecules involved in many physiological functions. These signaling
pathways involve the activation of metabolic nuclear receptors, mainly the BA sensor FXR, and the
dedicated membrane G protein-coupled receptor, GPBAR1 (TGR5). As a consequence, the discovery of
GPBAR1/FXR selective or dual modulators represents an important answer to the urgent demand of new
pharmacological opportunity for several human diseases including dyslipidemia, cholestasis, nonalcoholic
steatohepatitis, Type 2 diabetes and inflammation. Targeted oriented discovery of natural compounds and
medicinal chemistry manipulation have allowed the development of promising drug candidates.