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Updated: May 10, 2026

Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells
Published on: July 18, 2019
Discovery of Non-Carboxylic Steroidal FXR Agonist as a Promising Preclinical Candidate for Metabolic
Zhe Zhang1,2,3, Xiaomin Zheng3, Chuyu Dong3
1Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), South China University of Technology, Guangzhou 510000, China.
Abstract:
Metabolic dysfunction-associated steatohepatitis (MASH) presents a growing global health challenge, underscoring the need for effective therapies. Farnesoid X receptor (FXR) represents a promising therapeutic target against MASH. This study reported the rational design of a novel non-carboxylic steroidal FXR agonist, compound 27, which demonstrated effective FXR agonistic activity (TR-FRET: EC50 = 10 ± 3 nM; Luciferase Reporter: EC50 = 128 ± 9 nM) alongside reduced activation of the off-target receptor MRGPRX4 compared to OCA. Compound 27 exhibited high oral bioavailability in rats (F = 70.30%) and activation of hTGR5 (HTRF: EC50 = 1360 nM). In vivo studies confirmed its efficacy: attenuated collagen deposition in the CCl4-induced liver fibrosis model and improved steatosis and inflammatory foci in the MASH model. In summary, compound 27 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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