Therapeutics: Yes-associated protein 1 (YAP1; YAP); p21 protein (Cdc42 Rac)-activated kinase 1 (PAK1)

Cell culture and mouse studies suggest inhibiting YAP1 or PAK1 could help treat liver fibrosis. In activated rat primary liver myofibroblasts, the YAP1 inhibitor Visudyne verteporfin or a PAK1 inhibitor tool compound decreased collagen expression compared with vehicle. In activated human primary liver myofibroblasts, the PAK1 inhibitor decreased collagen expression. In mouse models of chemical-induced and bile duct ligation-induced liver fibrosis, Visudyne or the PAK1 inhibitor decreased collagen levels and fibrosis in the liver. Next steps could include testing identifying YAP1 inhibitors and testing PAK1 inhibitors in models of liver fibrosis.

Valeant Pharmaceuticals International Inc. and Novartis AG market Visudyne to treat choroidal neovascularization (CNV)...