NPD7426 suppresses sterol regulatory element-binding proteins by promoting the degradation of mature SREBP forms.

Abstract

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis, playing a central role in lipid metabolism regulation in vivo. SREBP-1c activity is significantly elevated in the liver under conditions of obesity, fatty liver disease, and type II diabetes, while suppression of SREBP-1c activity has been shown to alleviate these symptoms. Consequently, targeting SREBP-1c activity is considered a potential therapeutic approach for these conditions. In this study, we identified NPD7426 as a compound with inhibitory effects on SREBP activity. Furthermore, we demonstrated that NPD7426 promotes the proteasome-mediated degradation of mature SREBP protein forms. These findings provide new insights into the mechanism of SREBP activity suppression by small-molecule compounds containing NPD7426, suggesting that NPD7426 may be a promising candidate for the development of therapeutic drugs targeting SREBPs.