A Long-Acting Farnesoid X Receptor (FXR) Agonist Prevents Fibrosis

Authors

• Ashrafi Sultana, University of Nebraska Medical Center
• Grace Bybee, University of Nebraska Medical CenterFollow
• Anup S. Pathania, University of Nebraska Medical CenterFollow
• Weimin Wang, University of Nebraska Medical CenterFollow
• Nam Thai Hoang Le, University of Nebraska Medical CenterFollow
• Brandon W. Hanson, University of Nebraska Medical CenterFollow
• Christopher D. Bauer, University of Nebraska Medical CollegeFollow
• Deanna D. Mosley, University of Nebraska Medical CenterFollow
• Howard Gendelman, University of Nebraska Medical CenterFollow
• Samuel M. Cohen, University of Nebraska Medical CenterFollow
• Todd A. Wyatt, University of Nebraska Medical CenterFollow
• Larisa Y. Poluektova, University of Nebraska Medical CenterFollow
• Benson J. Edagwa, University of Nebraska Medical Center, OmahaFollow
• Natalia A. Osna, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Biomolecules

Publication Date

2026

Volume

16

Abstract

Despite effective vaccines and antiviral therapies, patients with chronic hepatitis B (CHB) remain at risk of developing progressive liver fibrosis and cirrhosis. Vonafexor (VON), a second-generation synthetic non-steroidal, non-bile acid farnesoid X receptor agonist, has been shown to prevent liver fibrosis and target the HBV cccDNA reservoir. However, adherence to daily oral therapy is an established barrier to successful treatment of chronic infections. To overcome this barrier, VON was transformed into a long-acting (LA) prodrug nanosuspension. The LA prodrug formulation suppressed αSMA, TGFβ, and Col1A1 gene expression in the LX2 hepatic stellate cell line. The formulation was well tolerated and prevented liver and lung damage in a carbon tetrachloride-induced chronic liver injury model. The promising preclinical data support further development of LA VON prodrugs as potential treatments for liver and lung fibrosis.

MeSH Headings

Receptors, Cytoplasmic and Nuclear, Receptor, Farnesoid X-Activated, Animals, Humans, Liver Cirrhosis, Prodrugs, Hepatic Stellate Cells, Carbon Tetrachloride, Cell Line, Mice, Collagen Type I, Transforming Growth Factor beta, Male

DOI Link

10.3390/biom16101443

ISSN

2218-273X

Recommended Citation

Sultana, Ashrafi; Bybee, Grace; Pathania, Anup S.; Wang, Weimin; Le, Nam Thai Hoang; Hanson, Brandon W.; Bauer, Christopher D.; Mosley, Deanna D.; Gendelman, Howard; Cohen, Samuel M.; Wyatt, Todd A.; Poluektova, Larisa Y.; Edagwa, Benson J.; and Osna, Natalia A., "A Long-Acting Farnesoid X Receptor (FXR) Agonist Prevents Fibrosis" (2026). Journal Articles: Environmental, Agricultural & Occupational Health. 29.
https://digitalcommons.unmc.edu/coph_env_articles/29