7030B-C5

7030B-C5 is a novel small-molecule transcriptional inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). Identified through a cell-based high-throughput screening platform, it down-regulates PCSK9 expression by modulating the transcription factors hepatocyte nuclear factor 1-alpha (HNF1α) and forkhead box protein O3 (FoxO3). This reduction in PCSK9 levels leads to an increase in total cellular low-density lipoprotein receptor (LDLR) protein and enhanced LDL-cholesterol (LDL-C) uptake. Preclinical studies in C57BL/6J and ApoE knockout mice have demonstrated that oral administration of 7030B-C5 reduces hepatic and plasma PCSK9 levels, increases hepatic LDLR expression, and inhibits atherosclerotic lesions. Furthermore, the compound appears to play a role in integrating hepatic glucose and lipid metabolism via FoxO1, suggesting potential utility in managing cholesterol/glucose homeostasis and cardiovascular disease.