A Novel FXR-Targeted DUBTAC and Its Applications in Cholestasis Therapy - PubMed
4 hours ago
- #cholestasis
- #DUBTAC
- #FXR
- Farnesoid X receptor (FXR) is crucial for treating cholestatic liver disease.
- FXR agonists often lose effectiveness due to protein degradation in pathological conditions.
- Discovery of FXR DUBTAC stabilizer D11 as a potential treatment for cholestasis.
- 31 novel compounds were synthesized by linking FXR ligands to OTUB1 ligand EN523.
- D11 increased FXR protein levels in HepG2 cells in a dose- and time-dependent manner.
- D11's action depends on a functional ubiquitin-proteasome system.
- D11 significantly raised hepatic FXR protein levels in mice with cholestasis liver injury.
- D11 showed excellent hepatoprotective effects and a reliable safety profile.
- D11 is a promising lead compound for FXR-targeted cholestasis therapy.
- The study suggests a new drug development approach by stabilizing the FXR receptor.