MD001

MD001 is a dual agonist of peroxisome proliferator-activated receptor ? (PPAR?) and PPAR?.1 It binds to PPAR? and PPAR? (Kds = 9.55 and 0.14 ?M, respectively) but does not bind to PPAR?/? at concentrations up to 500 ?M. It increases transcriptional activity of PPAR? and PPAR? in a cell-based luciferase reporter assay when used at a concentration of 10 ?M. MD001 (10 ?M) increases expression of PPAR?, PPAR?, and retinoid X receptor (RXR), as well as PPAR? and PPAR? target genes, in HepG2 cells. It increases glucose consumption as well as expression of GLUT2 and GLUT4 in HepG2 and 3T3-L1 cells, respectively, in a concentration-dependent manner. MD001 (20 mg/kg) decreases levels of glucose, insulin, free fatty acids, triglycerides, LDL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in blood and reduces the size and number of hepatic lipid droplets in diabetic db/db mice.