Nonacidic Farnesoid X Receptor Modulators

As a cellular bile
acid sensor, farnesoid X receptor (FXR) participates
in regulation of bile acid, lipid and glucose homeostasis, and liver
protection. Clinical results have validated FXR as therapeutic target
in hepatic and metabolic diseases. To date, potent FXR agonists share
a negatively ionizable function that might compromise their pharmacokinetic
distribution and behavior. Here we report the development and characterization
of a high-affinity FXR modulator not comprising an acidic residue.