fxr 1

Compound LE-77, known as FXR CES2 modulator 1, functions as a dual regulator that activates FXR and inhibits CES2. It effectively mitigates the intestinal toxicity of irinotecan.

FXR HSD17B13 modulator 1 (compound 6) is an effective modulator of FXR HSD17B13, playing a significant role in studies related to metabolic dysfunction-associated steatohepatitis (MASH).

FXR/TGR5 agonist 1 acts as an agonist on both FXR and TGR5 receptors and is utilized for treating fatty liver disease.

FXR antagonist 1 is a selective, orally active intestinal FXR antagonist with an IC50 value of 2.1 μM. FXR antagonist 1 antagonises intestinal FXR and selectively inhibits intestinal FXR signalling by feedback activation of hepatic FXR. FXR antagonist 1 can improve liver steatosis, inflammation and fibrosis in the NASH (non-alcoholic steatohepatitis) model and can be used to study NASH.

β-FXR antagonist 1 (C 12), an isomer of FXR antagonist 1, functions as an FXR antagonist [1].

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,

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

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

BAR502 is a dual GPBAR1 and FXR agonist (IC50s: 0.4 μM and 2 μM).

NR1H4 activator 1 is a potent and selective agonist of the Famesoid X Receptor (FXR).

HPG1860, an agonist of the farnesoid X receptor (FXR), induces luminescence in reporter gene assays utilizing HEK293T cells expressing human FXR, with an EC50 value of 18 nM. In vivo studies demonstrate that HPG1860 (administered at 1, 3, or 10 mg kg daily) reduces serum alanine aminotransferase (ALT) and total cholesterol levels in a mouse model of non-alcoholic steatohepatitis (NASH), which was induced by a high-fat diet and carbon tetrachloride (CCl4). Additionally, this compound decreases hepatic inflammation, fat levels, and fibrosis.

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)

CAY10771 is a dual agonist of farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor δ (PPARδ).1It activates FXR and PPARδ in reporter assays using HEK293T cells (EC50s = 0.94 and 1.5 μM, respectively) and is selective for these receptors over retinoic acid receptor α (RARα), retinoid X receptor α (RXRα), PPARα, PPARγ, and liver X receptor α (LXRα) at 10 μM. 1.Schierle, S., Neumann, S., Heitel, P., et al.Design and structural optimization of dual FXR/PPARδ activatorsJ. Med. Chem.63(15)8369-8379(2020)

BMS-986318 is a potent nonbile acid FXR agonist with EC50 values of 53 nM (FXR Gal4) and 350 nM (SRC-1 recruitment assays). It has a favorable ADME profile and demonstrates effectiveness in mouse models of liver cholestasis and fibrosis caused by bile duct ligation. BMS-986318 is used in research on nonalcoholic steatohepatitis.

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.

FXR agonist 4 with an EC 50 value of 1.05 μM. FXR agonist 4 effectively improves hyperlipidemia, hepatic steatosis, insulin resistance and hepatic inflammation in DIO mice. FXR agonist 4 can be used for the research of non-alcoholic fatty liver disease (NAFLD) .

Compound A-26, also known as FXR antagonist 2, is a diarylamide derivative that functions as a moderate FXR antagonist. It is utilized in researching hyperlipidemia and type 2 diabetes [1].

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].

ZLY28 is a novel, first-in-class compound with specific intestinal restriction and oral activity, serving as a dual modulator of FXR and FABP1. Additionally, it is a pioneering anti-NASH agent, utilized in the study of nonalcoholic steatohepatitis (NASH) [1].

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].

F44-A13 is an orally active, highly selective farnesoid X receptor (FXR) antagonist with an IC50 value of 1.1 μM. It optimizes cholesterol metabolism and reduces activity by inducing CYP7A1 expression, lowering cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels in mouse models. F44-A13 is applicable for studying metabolic diseases associated with lipid disorders [1].

Linafexor (CS-0159) acts as an agonist for the farnesoid X receptor (FXR) [1].

V023-9340 is a powerful FXR inhibitor with an IC50 of 4.27 μM, suitable for research in NASH (nonalcoholic steatohepatitis) [1].

XJ02862-S2 demonstrates potent FXR agonistic activity and is a promising lead compound for NAFLD research [1].