| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
Active metabolite of Obeticholic acid; phase II reaction product; farnesoid X receptor (FXR)
Glyco-Obeticholic acid targets the farnesoid X receptor (FXR), a nuclear receptor that regulates the expression of genes involved in bile acid, lipid, and glucose metabolism. As an active metabolite of the FXR agonist Obeticholic acid, it activates FXR signaling, modulating bile acid synthesis and metabolic homeostasis. |
|---|---|
| ln Vitro |
Microorganisms in the ileum and colon can cleave the sugar obeticholic acid and convert it into the parent drug, which can subsequently be reabsorbed or expelled in the feces. Obeticholic acid interacts with glycine in the liver to generate ethylene glycol obeticholic acid, which is released into the bile [1].
In vitro, Glyco-Obeticholic acid is an active metabolite of the FXR agonist Obeticholic acid. It activates FXR signaling, regulating gene expression involved in bile acid and lipid metabolism. It is used as a research tool to study FXR-mediated pathways in metabolic and liver diseases. |
| ln Vivo |
Obeticholic acid (OCA) is exemplified as a potent drug for treating primary biliary cirrhosis and nonalcoholic fatty liver disease by inhibiting bile acid synthesis. However, it remains unclear whether the effect of OCA is mediated by the function of brown adipose tissue (BAT). In the present study, brown adipogenesis differentiation in vitro and db/db mouse model treated with OCA were used to assess the anti-obesity function by body weight tracking, O2 consumption, food intake, physical activity, glucose tolerance tests. In addition, uncoupling protein 1 (Ucp1) protein expression in brown adipose tissue was measured by western blotting, morphometry of brown adipose tissue was analyzed by hematoxylin and eosin staining. Hepatic steatosis was detected by Oil-Red O staining and serological analysis was performed to assess the effect of OCA on hyperlipidemia. OCA treatment enhanced brown adipocyte cell differentiation and upregulated the expression of the BAT-specific gene Ucp1) in C3H10T1/2 cells in vitro. Consistent with these findings, OCA increased whole-body energy metabolism and glucose homeostasis by enhancing BAT activity in vivo, and ultimately decreased body weight gain in db/db mice. In addition, the results demonstrated that spontaneous hepatic steatosis in db/db mice was ameliorated following OCA treatment. In summary, OCA functioned as a BAT activator to help ameliorate obesity and maintain glucose homeostasis in db/db mice. The present results may provide a novel potential therapeutic approach to activate brown fat in patients with obesity and other metabolic disorders.https://pubmed.ncbi.nlm.nih.gov/34345273/
In vivo, Glyco-Obeticholic acid is an active metabolite of Obeticholic acid, formed by conjugation with glycine. It is secreted into bile and contributes to the overall pharmacological activity of the parent drug. Its role in vivo is primarily understood through pharmacokinetic and pharmacodynamic studies, where its concentration is correlated with FXR activation and metabolic effects. |
| Enzyme Assay |
In vitro assays for Glyco-Obeticholic acid typically involve measuring its activation of FXR. A luciferase reporter gene assay is used where cells are transfected with an FXR expression plasmid and a reporter plasmid containing FXR response elements. The compound is added at various concentrations, and luciferase activity is measured. EC50 values are calculated from dose-response curves.
|
| Cell Assay |
For in vitro cell-based assays, hepatocytes or other cells expressing FXR are cultured and treated with Glyco-Obeticholic acid at various concentrations. FXR activation is confirmed by measuring the expression of FXR target genes (e.g., SHP, BSEP, CYP7A1) by qRT-PCR. Cell viability is assessed by standard assays. The compound's effects on lipid and glucose metabolism can be assessed in relevant cell models.
|
| Animal Protocol |
In vivo animal studies with Glyco-Obeticholic acid are conducted in models of metabolic and liver diseases. The compound is administered orally to rodents. Efficacy is measured by assessing markers of bile acid metabolism, lipid profiles, and glucose homeostasis. Liver histology is examined for signs of fibrosis or steatosis. The compound's effects on FXR target gene expression are analyzed in liver tissues.
|
| ADME/Pharmacokinetics |
Glyco-Obeticholic acid (CAS: 863239-60-5) has a molecular weight of 477.68 g/mol and a molecular formula of C28H47NO5. Appearance: solid. Purity: ≥98%. Solubility: DMF: 20 mg/mL; DMSO: 10 mg/mL; Ethanol: 15 mg/mL. Storage: -20°C. The compound is a glycine-conjugated active metabolite of Obeticholic acid.
|
| Toxicity/Toxicokinetics |
Glyco-Obeticholic acid is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a FXR agonist metabolite, it may have effects on bile acid metabolism and liver function. Standard laboratory safety precautions should be followed when handling the compound.
|
| References |
[1]. Markham A, et al. Obeticholic Acid: First Global Approval. Drugs. 2016 Aug;76(12):1221-6.
|
| Additional Infomation |
We have previously demonstrated that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) can protect the liver by downregulating the expression of hepatic matrix metalloproteinases (MMPs), thereby preventing multi-organ dysfunction caused by ischemia/reperfusion (I/R) injury. This study aimed to investigate the ability of OCA to modulate MMPs in distal organs such as the kidneys. Male Wistar rats were orally administered OCA (10 mg/kg/day for 5 consecutive days) followed by 60 minutes of partial hepatic ischemia. 120 minutes after reperfusion, renal biopsy tissue (cortex and medulla) and blood samples were collected. Serum creatinine, renal MMP-2 and MMP-9 dimers, tissue inhibitors of MMPs (TIMP-1, TIMP-2), RECK, TNF-α, and IL-6 levels were measured. Following hepatic ischemia/reperfusion (I/R), MMP-9 dimer activity increased in the renal cortex and medulla, while MMP-9 dimer activity decreased in the renal cortex of I/R rats treated with OCA. Although the differences were not statistically significant, MMP-2 activity in the renal cortex of I/R rats in the OCA treatment group was also reduced. There were no significant differences in TIMPs and RECK levels among the groups. Serum creatinine increased after I/R, but decreased in the OCA treatment group. Tissue TNF-α and IL-6 levels showed the same trend. Although the underlying mechanism requires further investigation, this study is the first to reveal that OCA has a beneficial effect on the kidneys by reducing TNF-α-mediated MMP expression after hepatic I/R. https://pubmed.ncbi.nlm.nih.gov/35631351/
Glyco-Obeticholic acid is the glycine-conjugated active metabolite of Obeticholic acid (6-ECDCA), a potent FXR agonist. It has the CAS number 863239-60-5 and a molecular weight of 477.68 g/mol. It is used in research to investigate FXR signaling in metabolic and liver diseases. It is not FDA-approved and is intended for research use only. |
| Molecular Formula |
C28H47NO5
|
|---|---|
| Molecular Weight |
477.676489114761
|
| Exact Mass |
477.345
|
| Elemental Analysis |
C, 70.40; H, 9.92; N, 2.93; O, 16.75
|
| CAS # |
863239-60-5
|
| Related CAS # |
Glyco-obeticholic acid-d5
|
| PubChem CID |
121322333
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
5.1
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
34
|
| Complexity |
772
|
| Defined Atom Stereocenter Count |
11
|
| SMILES |
CC[C@@H]1[C@@H]2C[C@@H](CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3[C@@H]1O)CC[C@@H]4[C@H](C)CCC(=O)NCC(=O)O)C)C)O
|
| InChi Key |
MTLPUOZJBFHNSO-FCWTVGIUSA-N
|
| InChi Code |
InChI=1S/C28H47NO5/c1-5-18-22-14-17(30)10-12-28(22,4)21-11-13-27(3)19(7-8-20(27)25(21)26(18)34)16(2)6-9-23(31)29-15-24(32)33/h16-22,25-26,30,34H,5-15H2,1-4H3,(H,29,31)(H,32,33)/t16-,17-,18-,19-,20+,21+,22+,25+,26-,27-,28-/m1/s1
|
| Chemical Name |
2-[[(4R)-4-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-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
|
| Synonyms |
GlycoObeticholic acid; Glyco-obeticholic acid; 863239-60-5; Glyco-oca; 6-Egcdca; O2MZK6V9LQ; UNII-O2MZK6V9LQ; CHEMBL4072790; Glyco Obeticholic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0935 mL | 10.4673 mL | 20.9345 mL | |
| 5 mM | 0.4187 mL | 2.0935 mL | 4.1869 mL | |
| 10 mM | 0.2093 mL | 1.0467 mL | 2.0935 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
