ly-295427 and cholest-4-en-3-one

4 alpha-(2-Propenyl)-5 alpha-cholestan-3 alpha-ol (LY295427) was previously identified from a CHO cell-based assay to be a potent LDL receptor up-regulator and had demonstrated to be an effective agent in lowering plasma cholesterol levels in hypercholesterolemic hamsters. In order to investigate the effect of flexibility of the 3 alpha-hydroxy-bearing A-ring on the activity, 4 alpha-(2-propenyl)-5,6-secocholestan-3 alpha-ol (11), a B-ring seco analog of LY295427, is thus synthesized from cholest-4-en-3-one. Test results indicate that 11 is not active in the CHO cell-based LDL receptor/luciferase assay at concentrations up to 20 micrograms/mL. The result underlines the importance of maintaining the A-B-C-D ring rigidity of the 3 alpha-sterols in terms of binding to the putative oxysterol receptor.

Topics: Animals; Anticholesteremic Agents; CHO Cells; Cholestanol; Cholestanols; Cholestenones; Cricetinae; Gene Expression Regulation; Genes, Reporter; Hydroxycholesterols; Luciferases; Promoter Regions, Genetic; Receptors, LDL; Structure-Activity Relationship