(E)-Guggulsterone

Description: Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR bothin vitroandin vivo.4Thecisstereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50value of 15 µM.5,6By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.4. Target: Others. Smiles: [H][C@@]12CC(=O)\C(=C\C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C. References: Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999)