A novel cell-permeable LOXL2 inhibitor PAT-1251 potently suppresses biliary liver fibrosis via collagen crosslinking-dependent and -independent mechanisms
While having comparable extracellular effects on collagen crosslinking in vivo, the cell-permeable LOXL2 inhibitor PAT-1251 exerted potent antifibrotic activity in hepatic progenitors and HSC cultures compared with the anti-LOXL2 antibody. PAT-1251 substantially outperformed the anti-LOXL2 antibody in the BALB/c. Mdr2-/- model of biliary fibrosis, suggesting that intracellular LOXL2 targeting is therapeutically important in addition to its well-characterized extracellular collagen crosslinking activity.
Authors
- Yi‐Jun Lin (ORCID: https://orcid.org/0000-0001-9305-8911)
- Yury V. Popov (ORCID: https://orcid.org/0000-0001-7973-942X)
- Pinzhu Huang (ORCID: https://orcid.org/0000-0002-8339-9701)
- Jing Wang (ORCID: https://orcid.org/0000-0001-7199-4784)
- Ping An (ORCID: https://orcid.org/0000-0002-0018-2233)
- Wenda Li
- Guangyan Wei (ORCID: https://orcid.org/0000-0002-3137-1483)
- Heansika Matta
- Bain Gretchen
Institutions
- Beth Israel Deaconess Medical Center (US)
- Sun Yat-sen University (CN)
- Wuhan University (CN)
- MEI Pharma (United States) (US)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Renmin Hospital of Wuhan University (CN)
- aTyr Pharma (United States) (US)
Publication Details
- Journal
- Hepatology Communications
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1097/hc9.0000000000000863
- Primary Topic
- Liver physiology and pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00