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Repositioning an Immunomodulatory Drug Vidofludimus as a Farnesoid X Receptor Modulator With Therapeutic Effects on NAFLD.


ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disorder, and yet with no pharmacological treatment approved worldwide. The repositioning of old drugs provides a safe approach for drug development. Vidofludimus, an inhibitor for dihydroorotate dehydrogenase (DHODH) for the treatment of autoimmune disorders, is herein uncovered as a novel modulator for farnesoid X receptor (FXR) by biochemical and crystallographic analysis. We further revealed that vidofludimus exerts in vivo therapeutic effects on dextran sodium sulfate (DSS)-induced colitis in an FXR-dependent manner. Notably, vidofludimus also possesses remarkable beneficial effects in reducing NAFLD by targeting FXR, which may represent a unique approach in developing the treatment for NAFLD. Our findings not only reveal a promising template for the design of novel FXR ligands in treating autoimmune disorders, but also uncover a novel therapeutic effect for vidofludimus on NAFLD based on the newly established relationships among drugs, targets, and diseases.

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC7240069 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Repositioning an Immunomodulatory Drug Vidofludimus as a Farnesoid X Receptor Modulator With Therapeutic Effects on NAFLD.

Zhu Yanlin Y   Xu Shuangshuang S   Lu Yi Y   Wei Yijuan Y   Yao Benqiang B   Guo Fusheng F   Zheng Xing X   Wang Yumeng Y   He Ying Y   Jin Lihua L   Li Yong Y  

Frontiers in pharmacology 20200514


Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disorder, and yet with no pharmacological treatment approved worldwide. The repositioning of old drugs provides a safe approach for drug development. Vidofludimus, an inhibitor for dihydroorotate dehydrogenase (DHODH) for the treatment of autoimmune disorders, is herein uncovered as a novel modulator for farnesoid X receptor (FXR) by biochemical and crystallographic analysis. We further revealed that vidofludimus  ...[more]

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