Glycine-beta-muricholic Acid

Glycine-beta-muricholic acid (GbetaMCA) is an intestine-selective antagonist of the farnesoid X receptor (FXR) and the glycine-conjugated form of the murine-specific primary bile acid beta-muricholic acid (Cay-20287). It inhibits expression of the FXR target genes Shp and Fgf15 induced by the FXR ligands chenodeoxycholic acid (Cay-10011286) and GW 4064 (Cay-10006611) in Caco-2 cells when used at a concentration of 100 µM. GbetaMCA is resistant to hydrolysis by fecal bile salt hydrolase (BSH) isolated from gut microbiota, indicating gut stability. Dietary administration of GbetaMCA (10 mg/kg) decreases Shp and Fgf15 mRNA expression in ileum, but not liver, and reduces ceramide levels and expression of the ceramide synthesis-related genes Sptlc2, Sptlc3, Cers2, Cers4, Degs1, Degs2, Smpd3, and Smpd4 in ileum of mice with high-fat diet-induced obesity and db/db mice. It also prevents weight gain, reduces blood glucose levels, and increases insulin sensitivity as well as prevents development of cholestasis and necrotic lesions in liver of mice with high-fat diet-induced obesity.Formal Name: N-[(3alpha,5beta,6beta,7beta)-3,6,7-trihydroxy-24-oxocholan-24-yl]-glycine. CAS Number: 66225-78-3. Synonyms: Gly-MCA, GbetaMCA. Molecular Formula: C26H43NO6. Formula Weight: 465.6. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 20 mg/ml, Ethanol: 20 mg/ml. SMILES: O[C@@H]1CC[C@@]2(C)[C@@]([C@H](O)[C@H](O)[C@]3([H])[C@]2([H])CC[C@@]4(C)[C@@]3([H])CC[C@]4([H])[C@H](C)CCC(NCC(O)=O)=O)([H])C1. InChi Code: InChI=1S/C26H43NO6/c1-14(4-7-20(29)27-13-21(30)31)16-5-6-17-22-18(9-11-25(16,17)2)26(3)10-8-15(28)12-19(26)23(32)24(22)33/h14-19,22-24,28,32-33H,4-13H2,1-3H3,(H,27,29)(H,30,31)/t14-,15-,16-,17+,18+,19+,22+,23+,24-,25-,26-/m1/s1. InChi Key: ZQYUKJFJPJDMMR-IIWZPVADSA-N.