DC371739 is a lipid-lowering small compound that directly binds to HNF-1α with Kd of 2.3 uM in BLI assays and inhibit its dimerization, inhibits the transcription levels of both PCSK9 and ANGPTL3, displays promising hypolipidemic effects both in vitro and in vivo.
DC371739 interferes with the transcriptional function of HNF-1α by disrupting its binding to DNA.
DC371739 also inhibits HNF-1α target genes such as Dedicator of cytokinesis protein 3 (Dock3) and Zinc finger and BTB domain-containing protein 20 (Zbtb20).
DC371739 downregulates PCSK9 expression and upregulates LDLR expression both in vitro and in vivo.
DC371739 inhibits ANGPTL3 expression and enhances lipoprotein lipase activity both in vitro and in vivo.
Combination of DC371739 and atorvastatin shows an additive effect in lipid clearance both in vitro and in vivo.
DC371739 significantly decreases serum TC, LDL-C, and TG levels simultaneously in HFD-fed hamsters, and decreases serum TC and LDL-C levels in spontaneous hyperlipidemic rhesus monkeys and individuals with hypercholesterolemia.