Novel tricyclic glycal-based TRIB1 inducers that reprogram LDL metabolism in hepatic cells.

ABSTRACT: Increased expression of the Tribbles pseudokinase 1 gene (TRIB1) is associated with lower plasma levels of LDL cholesterol and triglycerides, higher levels of HDL cholesterol and decreased risk of coronary artery disease and myocardial infarction. We identified a class of tricyclic glycal core-based compounds that upregulate TRIB1 expression in human HepG2 cells and phenocopy the effects of genetic TRIB1 overexpression as they inhibit expression of triglyceride synthesis genes and ApoB secretion in cells. In addition to predicted effects related to downregulation of VLDL assembly and secretion these compounds also have unexpected effects as they upregulate expression of LDLR and stimulate LDL uptake. This activity profile is unique and favorably differs from profiles p

SUBMITTER: Nagiec MM 

PROVIDER: S-EPMC6247893 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature