PCSK9 is a serine protease mainly expressed in the liver and the intestine. It acts by reducing the amount of LDLR in hepatocytes. PCSK9 enzymatic activity permits its intracellular maturation, followed by secretion. Circulating PCSK9 binds the LDLR on the cell surface and is subsequently cointernalized together with the LDLR. PCSK9 can also bind the LDLR intracellularly. Thus, by virtue of its role as a major inhibitor of the LDLR, PCSK9 has emerged as a hot new drug target to treat hypercholesterolemia and coronary heart disease. SBC-115076 is an anti-PCSK9 compound.
In vitro: It was found that SBC-115076 could dose-dependently increase the DHLDL uptake, which was lower than that SBC-110034 did. Moreover, SBC-115076 could increase several folds of the intracellular LDLR level at 1.6 μM [1].
In vivo: SBC-115076 was observed to lower cholesterol levels in mice that were fed high fat diet. Results showed data obtained with SBC-115076 indicating a mean of 32% reduction in total cholesterol levels after two weeks relative to high fat diet animal levels and a mean 50% reduction toward return to regular diet cholesterol levels [1].
Clinical trial: Up to now, SBC-115076 is still in the preclinical development stage.
Reference:
[1] Anti-proprotein convertase subtilisin kexin type 9 (anti-pcsk9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases. Patent: WO 2014150326 A1