DC371739 is an effective oral PCSK9 inhibitor that decreases both PCSK9 and ANGPTL3 mRNA expression. It also reduces PCSK9 protein expression while enhancing that of LDLR. Given its properties, DC371739 has potential applications in the study of hyperlipidemia.

DC371739 enhances the uptake of DiI-LDL in HepG2 cells in a dose- and time-dependent manner (0-10 µM, 0-24 h). Additionally, it reduces the mRNA expression of PCSK9 and ANGPTL3 in HepG2 cells at concentrations ranging from 0-5 µM over time periods of 4, 24, and 48 hours. At higher concentrations (0-10 µM; 24 hours), DC371739 decreases PCSK9 protein expression and increases LDLR protein expression. Furthermore, with a targeted approach at 5µM for 24 hours, DC371739 inhibits the transcription and expression of ANGPTL3 by targeting HNF-1α.

When administered orally at doses of 10, 30, and 100 mg/kg daily for 21 days, DC371739 significantly lowered total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in the plasma of six-week-old healthy male Syrian golden hamsters (HFD-fed). The decrease was substantial across all dosages, with serum TC levels reducing by 29.46%, 35.65%, and 38.69% respectively. Additionally, LDL-C levels were significantly reduced by 23.25%, 31.04%, and 35.03% at each escalating dose, and TG levels dropped by 49.57%, 57.52%, and 78.16%, showcasing the compound's potent lipid-lowering effects.