fxr

Forskolin (Coleonol) is a natural product, an adenylate cyclase activator (EC50=0.5 μM). Forskolin increases cAMP levels, activates PXR and FXR, and induces autophagy. Forskolin produces positive inotropic effects in the heart, and has platelet anticoagulant and antihypertensive effects.

Ursodeoxycholic acid sodium (Sodium Ursodeoxycholate) is a naturally occurring secondary bile acid with anti-inflammatory and cytoprotective activities. Ursodeoxycholic acid sodium acts as signaling molecule, exerting its effects by interacting with bile acid activated receptors,

Lithocholic acid (3α-Hydroxy-5β-cholanic acid) is a bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.

Chenodeoxycholic acid (CDCA) is a bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.

Tauro-Obeticholic acid is an active Obeticholic acid metabolite. Obeticholic acid is an orally bioavailable agonist of farnesoid-X receptor (FXR).

Ursodeoxycholic acid (UDCA) can be used to dissolve gallstones and reduce cholesterol absorption.

Ferolin is an agonist of the farnesoid X receptor (FXR) with an EC50 of 0.56 µM. It inhibits the expression of inflammatory genes such as iNOS, IL-1β, and TNFα in an FXR-dependent manner.

Tauro-β-muricholic acid (TβMCA), a trihydroxylated bile acid, serves as a competitive and reversible FXR antagonist (IC50 = 40 μM) and demonstrates antiapoptotic effects by preventing bile acid-induced hepatocellular apoptosis and maintaining mitochondrial membrane potential [1][2].

Altenusin is a natural nonsteroidal fungal metabolite, as a novel selective agonist of FXR with an EC50 value of 3.2 ± 0.2 μM.

Hyodeoxycholic acid (NSC 60672) has been used in trials studying the treatment of Hypercholesterolemia.

Guggulsterone (Guggulsterone E&Z) E&Z is a 3-hydroxy steroid. It has a role as an androgen.

Nelumol A, and nelumal A show a potency comparable to the endogenous ligand, they may as a valuable potential novel lead compound in the search for FXR agonists.

Androsterone, a metabolic product of testosterone, can activate Farnesoid X Receptor (FXR).

Alismanol M, a protostane-type triterpenoid isolated from the rhizome of Alisma orientale, functions as a farnesoid X receptor (FXR) agonist with an EC50 value of 50.25 μM. It is utilized in researching cholestasis and nonalcoholic steatohepatitis [1].

1. Alisol B 23-acetate (Alisol B Acetate) produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. 2. Alisol B 23-acetate produces promotive effect on liver regeneration, due to FXR-mediated regulation of genes involved in hepatocyte proliferation and hepato-protection. 3. Alisol B 23-acetate produces a protective effect against CCl4-induced hepatotoxicity, due to FXR and STAT3-mediated gene regulation.

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 1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)