| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
Gly-beta-MCA targets the farnesoid X receptor (FXR), a nuclear receptor that plays a critical role in bile acid, lipid, and glucose metabolism. It functions as a potent and intestine-selective FXR antagonist, meaning it blocks FXR activation specifically in the intestinal tract. This intestinal selectivity is a key feature that distinguishes Gly-beta-MCA from other FXR modulators. By inhibiting intestinal FXR, the compound modulates the enterohepatic circulation of bile acids and influences metabolic pathways involved in energy homeostasis. The compound does not significantly affect systemic FXR activity, which contributes to its favorable safety profile and makes it a valuable tool for studying tissue-specific FXR functions.
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| ln Vitro |
Gly-β-MCA is a bile acid that exhibits strong intestinal-selective inhibition of the farnesoid X receptor (FXR) [1]. The hydrolysis of BSH is resisted by Gly-β-MCA (Gly-MCA) [1].
In vitro studies have demonstrated that Gly-beta-MCA is a highly effective and selective inhibitor of intestinal FXR. The compound shows resistance to bile salt hydrolase (BSH), an enzyme produced by gut bacteria that deconjugates bile acids, which contributes to its stability in the intestinal environment. This resistance to bacterial degradation ensures that Gly-beta-MCA maintains its activity in the gut. The compound's ability to inhibit FXR in intestinal cells has been characterized using cell-based reporter assays and FXR target gene expression analysis. Unlike some other FXR inhibitors, Gly-beta-MCA does not increase fecal LCN-2 levels, indicating that it does not induce intestinal inflammation. |
| ln Vivo |
Without causing systemic, hepatic, or intestinal toxicity in mice, Gly-β-MCA (Gly-MCA, oral, 10 and 50 mg/kg) prevents and controls diet-induced and hereditary obesity, insulin resistance, and hepatic steatosis [1]. It is possible that Gly-MCA does not cause intestinal inflammation because it does not raise fecal LCN-2 levels [1].
Gly-beta-MCA has been studied in various in vivo models of metabolic disease. Oral administration of Gly-beta-MCA (Gly-MCA) at 10 and 50 mg/kg prevents and treats diet-induced and genetic obesity in mice. The compound also improves insulin resistance and hepatic steatosis without causing systemic, hepatic, or intestinal toxicities. Importantly, Gly-MCA does not increase fecal LCN-2 levels, indicating that it does not induce intestinal inflammation. These findings support the therapeutic potential of intestinal FXR inhibition for the treatment of metabolic disorders such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease. |
| Enzyme Assay |
The in vitro receptor binding assays for Gly-beta-MCA typically involve measuring the antagonistic activity of the compound against FXR using cell-free or cell-based reporter systems. In cell-free assays, the binding affinity of Gly-beta-MCA to FXR can be assessed using techniques such as fluorescence polarization, surface plasmon resonance, or radioligand binding displacement assays. The compound's ability to inhibit FXR-mediated transcription is evaluated using luciferase reporter gene assays in FXR-expressing cell lines. The intestinal selectivity of the compound can be confirmed by comparing its activity in intestinal versus hepatic cell systems. These assays are essential for characterizing the compound's pharmacological profile and selectivity.
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| Cell Assay |
Cellular assays for Gly-beta-MCA typically utilize intestinal cell lines such as Caco-2 or LS174T cells that express FXR. Cells are treated with varying concentrations of Gly-beta-MCA in the presence or absence of FXR agonists such as chenodeoxycholic acid or GW4064. FXR activation is assessed by measuring the expression of FXR target genes, including small heterodimer partner (SHP) and fibroblast growth factor 19 (FGF19), using quantitative PCR. The compound's antagonistic activity is demonstrated by its ability to inhibit agonist-induced gene expression. These cell-based assays confirm the compound's activity as an intestinal FXR antagonist and allow for the determination of IC50 values.
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| Animal Protocol |
In vivo animal studies for Gly-beta-MCA are conducted in mouse models of metabolic disease. Diet-induced obesity (DIO) models are established by feeding mice a high-fat diet, and genetic obesity models such as ob/ob or db/db mice are also used. Gly-beta-MCA is administered orally at doses of 10 and 50 mg/kg, typically once or twice daily. Body weight, food intake, and glucose tolerance are monitored throughout the study. At the end of the study, tissues are collected for histopathological analysis, and blood samples are analyzed for metabolic parameters including glucose, insulin, and lipid profiles. Hepatic steatosis is assessed by liver histology and triglyceride content measurements.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of Gly-beta-MCA indicate that the compound has oral bioavailability and is stable in the intestinal tract. Its resistance to bile salt hydrolase (BSH) contributes to its stability in the gut environment. The compound's intestinal selectivity means that it is primarily active in the gut with limited systemic exposure, which reduces the risk of systemic side effects. For in vivo formulation, Gly-beta-MCA is soluble in DMSO at 50 mg/mL and can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline at 2 mg/mL. The compound should be stored at low temperature, protected from direct sunlight, with powder stable at -20degC for 3 years.
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| Toxicity/Toxicokinetics |
Toxicology studies in mice have demonstrated that Gly-beta-MCA is well-tolerated even at therapeutic doses. Oral administration at 10 and 50 mg/kg does not cause systemic, hepatic, or intestinal toxicities in mice. Importantly, the compound does not increase fecal LCN-2 levels, indicating that it does not induce intestinal inflammation, a potential concern with some FXR modulators. This favorable safety profile is attributed to the compound's intestinal selectivity, which limits systemic exposure and avoids off-target effects in the liver and other organs. The lack of detectable toxicity supports the continued development of intestinal FXR antagonists for metabolic disorders.
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| References | |
| Additional Infomation |
Gly-beta-MCA is a research compound used primarily for studying the role of intestinal FXR in metabolic diseases. Its mechanism of action involves antagonism of FXR in the intestine, which modulates bile acid homeostasis and influences metabolic pathways involved in energy balance and glucose metabolism. The compound is not approved for clinical use and is available only for research purposes. Gly-beta-MCA is particularly valuable for studying tissue-specific FXR functions because of its intestinal selectivity, which allows researchers to dissect the contributions of intestinal versus hepatic FXR to metabolic regulation. Its resistance to BSH degradation makes it a stable tool for in vivo studies.
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| Molecular Formula |
C26H43NO6
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|---|---|
| Molecular Weight |
465.623
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| Exact Mass |
465.309
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| CAS # |
66225-78-3
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| PubChem CID |
137333454
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
759
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| Defined Atom Stereocenter Count |
11
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| SMILES |
C[C@@H]([C@@]1([H])CC[C@@]2([H])[C@@]3([H])[C@]([C@]4(CC[C@@H](O)C[C@H]4[C@H](O)[C@@H]3O)C)([H])CC[C@]12C)CCC(NCC(O)=O)=O
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| InChi Key |
ZQYUKJFJPJDMMR-IIWZPVADSA-N
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| 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
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| Chemical Name |
2-[[(4R)-4-[(3R,5R,6S,7R,8S,9S,10R,13R,14S,17R)-3,6,7-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]acetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~214.77 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1477 mL | 10.7384 mL | 21.4767 mL | |
| 5 mM | 0.4295 mL | 2.1477 mL | 4.2953 mL | |
| 10 mM | 0.2148 mL | 1.0738 mL | 2.1477 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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