Selective targeting of endothelial and perivascular angiocrine ROCK2 treats liver fibrosis - PubMed
5 days ago
- #ROCK2 inhibitor
- #liver fibrosis
- #angiocrine signaling
- Liver fibrosis is a significant pathological process leading to death in hepatic diseases, including metabolic dysfunction-associated steatohepatitis (MASH).
- Upregulation of Rho-associated coiled-coil containing kinase 2 (ROCK2) in liver endothelial cells (ECs) and perivascular hepatic stellate cells (HSCs) causes vascular niche dysfunction and pro-fibrotic signaling.
- A selective ROCK2 inhibitor, TDI01, was developed, showing anti-fibrotic effects in preclinical models and human patients.
- TDI01 restored vascular phenotype and reduced fibrosis in rodent and minipig MASH models.
- Phase 1 and extended clinical trials demonstrated TDI01's favorable pharmacokinetics, safety, and a trend toward reducing liver fibrosis in patients.
- Targeting angiocrine ROCK2 may provide a new treatment for liver fibrosis.