Biological Activity
SB-204990 is a cell-permeable and orally available γ-lactone prodrug of the non-cell-permeable SB-201076 th at inhibits human and r at ATP citrate-lyase (Ki =1 μM against human and r at ACL) in a predominantly competitive manner with a small but significant uncompetitive component. SB-204990 treatment is shown to suppress the rate of cellular cholesterol and fatty acid synthesis in HepG2 cultures (by 91% & 82%, respectively, with 30 μM SB-204990), and display hypocholesterolaemic and hypolipidaemic efficacy in vivo when administered in the diet (0.05-0.25%, w/w; mice, rats, dogs).
