New insights into the suppression of inflammation and lipid accumulation by .

Atherosclerosis is one of the leading causes of disease and death worldwide. The identification of new therapeutic targets and agents is critical. is expressed in many tissues and is found at particularly high levels in adipose tissue (AT). suppresses inflammation (including , , , , , , , , , and ) by reducing pathway activation and AT immune cell infiltration. reduces lipid accumulation by regulating the liver X receptor response element () of the promoter, the -response element () of , and the axis. and sites are present in many cytokine and lipid metabolism gene promoters, which suggests that regulates these genes through these sites. is the center of the -mediated inhibition of the inflammatory response. suppresses expression by suppressing expression. Interestingly, inhibition also decreases lipid accumulation. A dual-targeting strategy of and could inhibit both inflammation and lipid accumulation. Dual-target compounds (including prodrugs) 1-5 exhibit nanomolar inhibition by targeting and , , or . However, the suppressing activity of these compounds is relatively low (IC > 300 nM). Compounds 6-14 suppress expression with IC values ranging from 1.8 nM to 38.6 nM. HS-276 is a highly selective, orally bioavailable inhibitor. Combined structural modifications of compounds using a prodrug strategy may enhance inhibition. This review focused on the role and mechanism of in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.