Fexaramine is an investigational compound which acts as an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

farnesoid X receptor The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high levels ...

(FXR), which is a bile acid-activated

nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...

that controls bile-acid synthesis, conjugation and transport, as well as lipid metabolism through actions in the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

and

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

. The first publication about fexaramine in 2003 showed it has 100-fold greater affinity for FXR than natural compounds and described the genomic targets and binding site on FXR.; When administered orally to mice, fexaramine produced selective actions through FXR receptors in the intestines. Consistent with the effects of other FXR agonist drugs, in a study in mice, oral fexaramine stimulated intestinal fibroblast growth factor 15 (

FGF15 Fibroblast growth factor 15 is a protein in mouse encoded by the ''Fgf15'' gene. It is a member of the fibroblast growth factor (FGF) family but, like FGF19, FGF21 and FGF23, has endocrine functions. FGF19 is the orthologous protein in humans. ...

) production and resulted in metabolic improvements. Intestinal tissue-specific actions of fexaramine were suggested to be a possible new approach for the treatment of obesity and metabolic syndrome. However it cannot be determined from these preliminary results in mice whether FXR agonism with fexaramine will produce weight loss in humans. There are no clinical trials of fexaramine planned in humans and therapy with such FXR agonists for obesity is only a theoretical approach.

References

{{FXR and LXR modulators Cyclohexyl compounds Farnesoid X receptor agonists