Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic Dysfunction-Associated Steatohepatitis

Zhe Zhang; Xiaomin Zheng; Chuyu Dong; Pengru Li; Yi Lin; Zhenzhu Sun; Wenjing Li; Xiaoxiao Liu; J J Li; S Li; Bing Gu; Lei Zhang

doi:10.1021/acs.jmedchem.5c03220

May 8, 2026Journal of Medicinal Chemistry

Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic Dysfunction-Associated Steatohepatitis

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Key Points

The aim is to evaluate the efficacy and safety of a non-carboxylic steroidal FXR agonist for metabolic dysfunction-associated steatohepatitis.
Dual-path strategy applied to enhance FXR and TGR5 activity.
MRGPRX4 suppression evaluated as part of the therapeutic profile.
Demonstrated promising efficacy with enhanced FXR/TGR5 activity.
Supported safety profile with MRGPRX4 suppression, indicating potential as a therapeutic agent.

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Implication

Preclinical trial uncovers a novel FXR agonist that improves outcomes in metabolic dysfunction-associated steatohepatitis, suggesting new treatment avenues.

Abstract

achieves its promising efficacy and safety profile by the dual-path strategy that enhances FXR/TGR5 activity while suppressing MRGPRX4, supporting its further development as a novel therapeutic agent for MASH.

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Cite This Study

Zhang et al. (2026) studied this question.

synapsesocial.com/papers/6a0171983a9f334c28271c38 https://doi.org/10.1021/acs.jmedchem.5c03220

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Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic Dysfunction-Associated Steatohepatitis

Key Points

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Implication

Abstract

Discussion

Cite This Study

Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic Dysfunction-Associated Steatohepatitis

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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