Farnesoid
X receptor (FXR) is an important regulator of bile acid,
lipid, amino acid, and glucose homeostasis, hepatic inflammation,
regeneration, and fibrosis. FXR has been recognized as a promising
drug target for various metabolic diseases such as lipid disorders,
nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis
(NASH), and chronic kidney disease. A large number of FXR ligands
have been developed by pharmaceutical companies and academic institutions,
and several candidates have progressed into clinical trials in the
past decade. However, it is continually a challenge to discover drugs
targeting FXR due to side effects associated with long-term administration.
In this perspective, we summarize the research progress on medicinal
chemistry of FXR modulators from 2018 to the present by discussing
the diverse structures of synthetic FXR modulators including steroidal
and non-steroidal ligands, their structure–activity relationships
(SARs), and their therapeutic applications.
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