title: Steroidal scaffolds as FXR and GPBAR1 ligands: from chemistry to therapeutical application.
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.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sepe
authors.affiliation: Hospital S. Maria della Misericordia, Perugia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Distrutti
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.|Institute of Computational Science, Faculty of Informatics, Università della Svizzera Italiana (USI), Lugano, Switzerland.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Limongelli
authors.affiliation: Department of Experimental & Clinical Medicine, University of Perugia, Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiorucci
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Zampella
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry* / Q000378:metabolism; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D001688:Biological Products; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D013256:Steroids; D013729:Terpenes; D000099150:Receptor, Farnesoid X-Activated; C473772:GPBAR1 protein, human