BSH inhibitor GR-7 (Gut restricted-7) is a potent, specific, covalent inhibitor of gut bacterial bile salt hydrolase (BSH) with IC50 of 237-1070 nM.
GR-7 selectively labels the B. theta BSH at Cys2.
GR-7 displays minimal off-target effects, does not affect farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), shows limited off-target activity against other bacterial proteins or mammalian proteins in intestinal cells.
GR-7 (10 uM) inhibits BSHs in bacterial culture.
GR-7 can inhibit gut bacterial BSH activity and modulate the bile acid pool in vivo while not significantly affecting the gut bacterial community.
GR-7 reduces ursodeoxycholic acid (UDCA) level and GLP-1 production in mice fed with normal chow or a high-fat diet.
GR-7 markedly reduced hepatic steatosis and inflammation in diet induced mouse model of steatohepatitis.
