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Peer-reviewedCC BY 4.0Biomolecules

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

  • Ashrafi Sultana1
  • Grace Bybee2
  • Anup S. Pathania2
  • Weimin Wang2
  • Nam Thai Hoang Le2
  • Brandon W. Hanson2
  • Christopher D. Bauer3
  • Deanna D. Mosley3
  • Howard E. Gendelman2
  • Samuel M. Cohen4
  • Todd A. Wyatt3,5,6
  • Larisa Y. Poluektova2
2 more authors
  • Benson J. Edagwa2
  • Natalia A. Osna2
6 affiliations
  1. 1Medical Sciences Interdepartmental Area Program, University of Nebraska Medical Center, Omaha, NE 68198, USA
  2. 2Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA
  3. 3Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198, USA
  4. 4Department of Pathology, Microbiology and Immunology, and Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
  5. 5Department of Internal Medicine, Pulmonary, Critical Care and Sleep Medicine Division, University of Nebraska Medical Center, Omaha, NE 68198, USA
  6. 6Veterans Affairs Nebraska-Western Iowa Health Care System, Research Service, 4101 Woolworth Avenue, Omaha, NE 68105, USA
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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.

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Cite

BibTeXRIS
BibTeX
@article{sultana2026longacting,
  title = {{A Long-Acting Farnesoid X Receptor (FXR) Agonist Prevents Fibrosis}},
  author = {Ashrafi Sultana and Grace Bybee and Anup S. Pathania and Weimin Wang and Nam Thai Hoang Le and Brandon W. Hanson and Christopher D. Bauer and Deanna D. Mosley and Howard E. Gendelman and Samuel M. Cohen and Todd A. Wyatt and Larisa Y. Poluektova and Benson J. Edagwa and Natalia A. Osna},
  journal = {Biomolecules},
  year = {2026},
  month = oct,
  doi = {10.3390/biom16101443},
  url = {https://www.mdpi.com/2218-273X/16/10/1443},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A Long-Acting Farnesoid X Receptor (FXR) Agonist Prevents Fibrosis
AU  - Ashrafi Sultana
AU  - Grace Bybee
AU  - Anup S. Pathania
AU  - Weimin Wang
AU  - Nam Thai Hoang Le
AU  - Brandon W. Hanson
AU  - Christopher D. Bauer
AU  - Deanna D. Mosley
AU  - Howard E. Gendelman
AU  - Samuel M. Cohen
AU  - Todd A. Wyatt
AU  - Larisa Y. Poluektova
AU  - Benson J. Edagwa
AU  - Natalia A. Osna
PY  - 2026
DA  - 2026/10/01
JO  - Biomolecules
DO  - 10.3390/biom16101443
UR  - https://www.mdpi.com/2218-273X/16/10/1443
AB  - 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.
SN  - 2218-273X
ER  -