bile acid receptor

Maralixibat Chloride (LUM001 chloride), an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation.

Chenodeoxycholic acid (CDCA) is a bile acid that inhibits 11β-HSD2 with an IC50 value of 22 mM. Chenodeoxycholic acid acts as a detergent to dissolve fat for intestinal absorption and is reabsorbed by the small intestine. Chenodeoxycholic acid is used as a choledocholithiasis, choledocholithiasis and laxative, as well as to prevent or dissolve gallstones.

L-692429 (MK-0751) is a potent nonpeptidyl growth hormone secretagogue (GHS) agonist and benzolactam derivative, known for reversing glucocorticoid-induced inhibition of GH secretion. L-692429 exhibits high affinity for the G protein-coupled receptor and is useful in studying acromegaly and obesity.

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) is a potent inhibitor of liver-specific fatty acid transporter 5 (FATP5). Ursodeoxycholic acid inhibits cholesterol absorption and is used to dissolve gallstones.

Triamterene is a barosensitive epithelial sodium channel (ENaC) blocker with a diuretic effect. It can also act as an inhibitor of the TGR5 receptor, reducing GLP-1 secretion and cAMP level increases induced by TGR5 activation in a dose-dependent manner.

Deoxycholic acid (Cholanoic Acid) is a bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.

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

Deoxycholic acid sodium salt (Sodium deoxycholate) can activate the G protein-coupled bile acid receptor TGR5 that stimulates brown adipose tissue (BAT) thermogenic activity.

Chenodeoxycholic Acid sodium salt (CDCA sodium salt) is a bile acid in humans that activates the nuclear receptor FXR, rescues axonal degeneration of induced pluripotent stem cell-derived neurons in patients with spastic paraplegia type 5 and cerebral xanthomatosis, and can be used to study pancreatic necrosis.

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

7α-Hydroxy-4-cholesten-3-one is an intermediate in bile acid synthesis from cholesterol, a PXR agonist, and a biomarker for bile acid loss and diseases related to defective bile acid biosynthesis. It is also the physiological substrate for [CYP8B1].

Gly-β-MCA is an orally bioactive, enteroselective and potent inhibitor of the farnesoid X receptor (FXR), a bile acid, used in the study of obesity and diabetes.

3-Oxo-5β-cholanoic acid (Dehydrolithocholic acid) is a bile acid metabolite that inhibits TH17 cell differentiation by directly binding to the transcription factor RORγt with a Kd of 1.13 μM.

TGR5 is a potent TGR5(GPCR19) agonist.

N-Lithocholyl-L-alanine, a bile acid conjugate, also serves as an inhibitor of the ephrin type-A receptor 2 (EPHA2) with an IC50 value of 19.95 µM.

LTD4 antagonist 2 (compound 6) functions as a leukotriene D4 (LTD4) antagonist with an IC50 of 2.8 μM for the cysteinyl leukotriene 1 receptor (CysLT1R). Additionally, it acts as an agonist for the G protein-coupled bile acid receptor 1 (GPBAR1), making it applicable for research into colitis, metabolic syndrome, and other GPBAR1- and CysLT1R-related diseases.

TGR5 agonist 7 (Compound 22-Na) is an intestine-restricted, orally active agonist of the G protein-coupled bile acid receptor TGR5 (GPBAR1 or GPR131) with an EC50 of less than 1 μM. In mouse models, it demonstrates blood glucose-lowering effects, making it useful for diabetes research.

MI-883 is an orally active Constitutive Androstane Receptor (CAR, EC50=73 nM) agonist and a Pregnane X Receptor (PXR, IC50=0.1 μM) antagonist. It enhances CAR LBD assembly (EC50=0.38 µM) and activates the CAR3 variant (EC50=0.074 µM), inducing CYP2B6 mRNA expression in HepaRG and primary human hepatocytes. Additionally, MI-883 inhibits the basal activity of PXR (IC50=2.03 µM) and reduces CYP3A4 mRNA expression in transiently transfected HepG2 cells. It also regulates cholesterol metabolism and bile acid excretion, improving hypercholesterolemia in mouse models.

5β-Cholestane-3α,7α,12α,25-tetrol is a type of bile acid alcohol that activates the G protein-coupled bile acid receptor 1 (GPBAR1), also known as TGR5, in HEK293 cells that express the human receptor, at concentrations between 0.1 to 10 µM. In individuals with cerebrotendinous xanthomatosis (CTX), a progressive metabolic leukodystrophy, levels of this compound are elevated in the blood, feces, and bile.

Hyodeoxycholic acid sodium salt, a natural secondary bile acid, enhances high-density lipoprotein function, reduces farnesoid X receptor antagonist bile acids, and induces potent cytotoxicity, apoptosis, and IL-8 synthesis.

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)

Norcholic Acid (Nor Cholic Acid) is a bile acid that promotes tumor progression and immune escape by modulating the farnesol X receptor in hepatocellular carcinoma.Norcholic Acid is efficiently absorbed from the intestine and is rapidly secreted into the bile.

Tauro-α-muricholic acid (TαMCA) is an antagonist of the farnesoid X receptor (FXR; IC50 = 28 μM) and a taurine-conjugated form of the murine-specific primary bile acid α-muricholic acid . TαMCA is common in rodents but has also been found in small amounts in human serum.