Proprotein convertase subtilisin kexin 9 (PCSK9) is a member of the subtilisin serine protease family with important roles in lipoprotein metabolism. PCSK9 overexpression in wild-type mice doubles plasma total cholesterol, possibly through acceleration of degradation of the LDL receptor (LDLR). SBC-115076 is an inhibitor of PCSK9 action that blocks LDLR degradation in HEK293T cells expressing PCSK9. Through this mechanism, submicromolar concentrations of SBC-115076 increase the uptake of LDL by liver cells in vitro. SBC-115076 is effective in vivo, lowering cholesterol levels in mice that are fed a high fat diet.
