Biomaterial Database

Chemistry and Pharmacology of GPBAR1 and FXR Selective Agonists, Dual Agonists, and Antagonists. 2019

Simona De Marino, and Carmen Festa, and Valentina Sepe, and Angela Zampella

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

In the recent years, bile acid receptors FXR and GPBAR1 have attracted the interest of scientific community and companies, as they proved promising targets for the treatment of several diseases, ranging from liver cholestatic disorders to metabolic syndrome, inflammatory states, nonalcoholic steatohepatitis (NASH), and diabetes.Consequently, the development of dual FXR/GPBAR1 agonists, as well as selective targeting of one of these receptors, is considered a hopeful possibility in the treatment of these disorders. Because endogenous bile acids and steroidal ligands, which cover the same chemical space of bile acids, often target both receptor families, speculation on nonsteroidal ligands represents a promising and innovative strategy to selectively target GPBAR1 or FXR.In this review, we summarize the most recent acquisition on natural, semisynthetic, and synthetic steroidal and nonsteroidal ligands, able to interact with FXR and GPBAR1.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001647	Bile Acids and Salts	Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.	Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile
D043562	Receptors, G-Protein-Coupled	The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.	G Protein Coupled Receptor,G-Protein-Coupled Receptor,G-Protein-Coupled Receptors,G Protein Coupled Receptors,Receptor, G-Protein-Coupled,Receptors, G Protein Coupled
D018160	Receptors, Cytoplasmic and Nuclear	Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.	Cytoplasmic Receptor,Cytoplasmic and Nuclear Receptors,Cytosolic and Nuclear Receptors,Hormone Receptors, Cytoplasmic,Hormone Receptors, Nuclear,Nuclear Hormone Receptor,Nuclear Receptor,Nuclear and Cytoplasmic Receptors,Cytoplasmic Hormone Receptors,Cytoplasmic Receptors,Cytosol and Nuclear Receptors,Intracellular Membrane Receptors,Nuclear Hormone Receptors,Nuclear Receptors,Receptors, Cytoplasmic,Receptors, Cytosol and Nuclear,Receptors, Cytosolic and Nuclear,Receptors, Intracellular Membrane,Receptors, Nuclear,Receptors, Nuclear and Cytoplasmic,Hormone Receptor, Nuclear,Membrane Receptors, Intracellular,Receptor, Cytoplasmic,Receptor, Nuclear,Receptor, Nuclear Hormone,Receptors, Cytoplasmic Hormone,Receptors, Nuclear Hormone