| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
Estradiol 17-(beta-D-Glucuronide) primarily targets the organic anion transporting polypeptides OATP1B1 and OATP1B3, which are expressed on the basolateral membrane of hepatocytes and mediate the hepatic uptake of this conjugated estrogen metabolite from the blood. It also interacts with the canalicular bile salt export pump (BSEP, ABCB11) and other transporters involved in bile acid homeostasis. The compound inhibits BSEP-mediated bile acid transport into bile, leading to the accumulation of bile acids in hepatocytes and subsequent cholestatic liver injury. In addition, E217G activates various signaling pathways that contribute to cholestasis, including disruption of tight junctions and altered actin cytoskeleton organization in hepatocytes.
|
|---|---|
| ln Vitro |
In vitro, Estradiol 17-(beta-D-Glucuronide) is used as a high-affinity substrate to study OATP transporter function and specificity in hepatocyte uptake assays. The compound is also used to induce cholestasis in primary human hepatocytes and hepatoma cell lines (e.g., HepG2, Huh7). At concentrations of 10-100 uM, E217G decreases bile acid uptake via BSEP, disrupts canalicular membrane integrity, and increases intracellular bile acid accumulation. The compound also induces oxidative stress and activates inflammatory signaling pathways (NF-kappaB, JNK) in hepatocytes. These properties make E217G a valuable tool for studying mechanisms of drug-induced liver injury and cholestasis.
|
| ln Vivo |
In vivo, administration of Estradiol 17-(beta-D-Glucuronide) to rodents induces intrahepatic cholestasis, characterized by decreased bile flow (cholestasis), elevated serum bile acids, and increased serum markers of liver injury such as ALT and ALP. This model is widely used to study the pathophysiology of estrogen-induced cholestasis, which occurs in human pregnancy and during oral contraceptive use. In rat models, E217G is administered intravenously at doses of 5-20 umol/kg, resulting in rapid onset of cholestasis within minutes. The cholestatic effect is reversible and has been shown to be alleviated by co-administration of tauroursodeoxycholic acid (TUDCA). E217G also alters the expression of hepatic transporters and tight junction proteins.
|
| Enzyme Assay |
For non-cellular assays (transporter studies), OATP1B1 and OATP1B3 activity is measured using membrane vesicles or transporter-overexpressing cells. For example, HEK293 cells stably expressing OATP1B1 are incubated with Estradiol 17-(beta-D-Glucuronide) (0.1-100 uM) in uptake buffer (HBSS, pH 7.4) at 37degC for 5-60 minutes. Uptake is stopped by adding ice-cold buffer, and cells are lysed. Compound concentration is measured by LC-MS/MS. For BSEP inhibition studies, inside-out membrane vesicles from BSEP-expressing cells are incubated with [3H]-taurocholate (10 uM) and E217G (1-100 uM) in assay buffer (50 mM HEPES, 100 mM sucrose, 100 mM KCl, pH 7.4) for 10 minutes at 37degC. The reaction is filtered through nitrocellulose membranes, and radioactivity is measured. For cholestasis mechanism studies, no standard cell-free assays are routinely used.
|
| Cell Assay |
For cell-based assays, primary human hepatocytes or HepG2 cells are seeded in 6-well plates (1×10⁶ cells/well) in Williams‘ Medium E with 10% FBS. After 24-48 hours, cells are treated with Estradiol 17-(beta-D-Glucuronide) (10-200 uM) for 4-24 hours. Bile canaliculi formation is assessed by staining with F-actin (phalloidin). Intracellular bile acid levels are measured using an enzymatic cycling assay or by LC-MS/MS. BSEP protein expression and localization are assessed by Western blot and immunofluorescence. Apoptosis is measured by caspase-3/7 activity (luminescence assay). Cytokine production (IL-6, TNF-alpha) is measured by ELISA. For transporter functional studies, OATP-overexpressing cells are used as described above.
|
| Animal Protocol |
For in vivo animal experiments, male Sprague-Dawley rats (8-10 weeks old) are used. Estradiol 17-(beta-D-Glucuronide) is dissolved in saline or DMSO and administered intravenously at a dose of 5-20 umol/kg body weight. Bile flow is measured by bile duct cannulation: a polyethylene catheter is inserted into the common bile duct, and bile is collected in pre-weighed tubes every 10-30 minutes for 2 hours. Bile flow (uL/min/g liver) is calculated. Blood samples are collected at multiple time points for measurement of serum bile acids (enzymatic assay), ALT, AST, ALP, and bilirubin. At the end of the experiment, liver tissue is collected for histological analysis (H&E staining, neutrophil infiltration), immunohistochemistry (BSEP, MRP2, tight junction proteins), and gene expression analysis (qPCR for inflammatory and transporter genes). In some studies, co-treatment with tauroursodeoxycholic acid (TUDCA, 50-100 mg/kg) is used to assess cholestasis alleviation.
|
| ADME/Pharmacokinetics |
Estradiol 17-(beta-D-Glucuronide) has a molecular weight of 448.51 and appears as a white to off-white solid powder. It is soluble in DMSO (may require sonication) and has limited solubility in water (slightly soluble). The compound should be stored as a powder at -20degC for up to 3 years, and in solution at -80degC for up to 6 months or at -20degC for up to 1 month. The glucuronide conjugate is more water-soluble than the parent estrogen, facilitating renal and biliary excretion. In aqueous solutions, it is stable at neutral pH but may undergo hydrolysis under acidic or basic conditions. Standard handling procedures for steroid conjugates should be followed.
|
| Toxicity/Toxicokinetics |
Estradiol 17-(beta-D-Glucuronide) has low acute toxicity at physiological concentrations (it is a normal human metabolite). However, at high concentrations, it induces cholestasis and liver injury as described in animal studies. In research settings, doses that induce cholestasis (5-20 umol/kg IV in rats) cause reversible liver dysfunction without significant mortality. No chronic toxicity studies have been reported. The compound should be handled as a potential endocrine disruptor, and standard laboratory safety precautions for handling steroid hormones should be followed (use of PPE, avoid inhalation/ingestion). It is not classified as a hazardous substance at typical research concentrations.
|
| References |
|
| Additional Infomation |
17β-estradiol-17-glucuronic acid is a steroidal uronic acid composed of a 17β-estradiol molecule linked to a β-glucuronic acid residue at the 17-position via a glycosidic bond. It is a steroidal uronic acid and also a 3-hydroxysteroid. Functionally, it is related to 17β-estradiol. It is the conjugate acid of 17β-estradiol-17-glucuronic acid.
Estradiol 17-(beta-D-Glucuronide) is a research compound and endogenous metabolite, not an approved drug. No clinical trials have been conducted with this compound for therapeutic use. Its primary research applications include studying mechanisms of intrahepatic cholestasis (particularly estrogen-induced cholestasis during pregnancy and oral contraceptive use), investigating OATP transporter function and substrate specificity, and as a tool for understanding drug-induced liver injury (DILI). The compound is also used in studies of enterohepatic circulation of estrogen metabolites and in the development of cholestasis therapies (e.g., evaluation of TUDCA and other bile acid-based treatments). It is classified as an endogenous metabolite and is available for research use only. |
| Molecular Formula |
C24H32O8
|
|---|---|
| Molecular Weight |
448.51
|
| Exact Mass |
448.21
|
| CAS # |
1806-98-0
|
| PubChem CID |
5281887
|
| Appearance |
White to off-white solid powder
|
| Vapour Pressure |
2.34E-20mmHg at 25°C
|
| LogP |
1.525
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
32
|
| Complexity |
716
|
| Defined Atom Stereocenter Count |
10
|
| SMILES |
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)C(=O)O)O)O)O)CCC5=C3C=CC(=C5)O
|
| InChi Key |
MTKNDAQYHASLID-QXYWQCSFSA-N
|
| InChi Code |
InChI=1S/C24H32O8/c1-24-9-8-14-13-5-3-12(25)10-11(13)2-4-15(14)16(24)6-7-17(24)31-23-20(28)18(26)19(27)21(32-23)22(29)30/h3,5,10,14-21,23,25-28H,2,4,6-9H2,1H3,(H,29,30)/t14-,15-,16+,17+,18+,19+,20-,21+,23-,24+/m1/s1
|
| Chemical Name |
(2S,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[[(8R,9S,13S,14S,17S)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]oxy]oxane-2-carboxylic 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 | 2.2296 mL | 11.1480 mL | 22.2960 mL | |
| 5 mM | 0.4459 mL | 2.2296 mL | 4.4592 mL | |
| 10 mM | 0.2230 mL | 1.1148 mL | 2.2296 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
