Biomimetic Total Synthesis and the Biological Evaluation of Natural Product (-)-Fargesone A as a Novel FXR Agonist.

ABSTRACT: Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, plays an important role in maintaining or reversing metabolic homeostasis during the development of liver diseases. However, developing FXR modulators to intervene in FXR-related diseases is still an unmet clinical need. Therefore, it is significant to develop novel small-molecule agonists for drug discovery targeting FXR. Through a high-throughput chemical screen and follow-up biological validations, we first identified the natural product Fargesone A (FA) as a potent and selective FXR agonist. The limited, variable supply of FA from natural product isolation, however, has impeded its biological exploration and potential drug development. Accordingly, we have developed a biomimetic and scalable total synthesis of FA

SUBMITTER: Guo F 

PROVIDER: S-EPMC9795464 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature