| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Fulvestrant metabolite; glucuronide conjugates of Fulvestrant
The primary target of A3334 is the CXXC5 (CXXC finger protein 5) and DVL (Dishevelled) interaction. By specifically inhibiting this protein-protein interface, A3334 prevents CXXC5 from acting as a negative feedback regulator of the Wnt/beta-catenin pathway, thereby activating downstream signaling that is crucial for metabolic regulation and cellular differentiation. |
|---|---|
| ln Vitro |
In vitro, A3334 (1-10 microM) effectively suppresses the adipogenic differentiation of 3T3-L1 preadipocytes by modulating the Wnt/beta-catenin signaling pathway. Additionally, treatment with A3334 (1-10 microM; 24 h) significantly enhances TOPFlash reporter activity in HEK293-TOP cells, confirming its ability to activate Wnt/beta-catenin transcription in a cellular context.
|
| ln Vivo |
In vivo, oral administration of A3334 (25 mg/kg; p.o. once daily) demonstrates significant anti-obesity effects in HFD-fed mice over 16 weeks without impacting normal diet-fed controls. A 5-day regimen notably decreases fasting glucose and improves glucose tolerance (GTT) and insulin tolerance (ITT). A 3-week course abolishes hepatosteatosis and reduces elevated ALT and AST levels in mouse models of obesity and NASH.
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| Enzyme Assay |
The non-cellular assay for A3334 involves a protein-protein interaction (PPI) inhibition assay using recombinant CXXC5 and DVL proteins. An FITC-labeled DVL peptide (FITC-DVL) is incubated with the CXXC5 protein in the presence of varying concentrations of A3334. The reaction is measured using a homogeneous time-resolved fluorescence (HTRF) or fluorescence polarization (FP) reader. The reduction in signal is used to calculate the IC50 of 63.06 nM for disrupting the CXXC5-DVL complex.
|
| Cell Assay |
The primary cellular assay uses HEK293-TOP cells, which harbor a stably integrated TOPFlash luciferase reporter responsive to Wnt/beta-catenin activation. Cells are seeded in 96-well plates and treated with A3334 at concentrations ranging from 1 to 10 microM for 24 hours. Following treatment, cells are lysed, and luciferase activity is measured using a luminescence plate reader. An increase in relative luminescence units (RLU) indicates successful activation of the Wnt pathway via CXXC5-DVL inhibition.
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| Animal Protocol |
In the animal model, 6-week-old male C57BL/6N mice are fed a high-fat diet (HFD) for 16 weeks to induce obesity and NASH. A3334 is administered orally at a dose of 25 mg/kg once daily for the duration of the study. Body weight and food intake are monitored weekly. At study endpoint, serum is collected for glucose, insulin, ALT, and AST analysis. Liver tissues are harvested for histology (H&E and Oil Red O staining) to assess steatosis, and adipose tissues are analyzed for adipocyte size and inflammation markers.
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| ADME/Pharmacokinetics |
A3334 is orally active and can be formulated for in vivo studies using a vehicle of 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% saline. It is soluble in DMSO at 250 mg/mL (813.54 mM). Specific parameters such as half-life, Cmax, and bioavailability have not been fully published, but its robust oral efficacy suggests adequate absorption and systemic exposure following oral administration in rodent models.
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| Toxicity/Toxicokinetics |
Specific toxicological data for A3334 is limited; however, studies report that administration of A3334 (25 mg/kg; p.o. once daily for 16 weeks) has no observable adverse effects on mice fed a normal diet, suggesting a favorable safety window. At effective doses in disease models, no overt signs of toxicity or mortality have been reported. Standard safety precautions for handling research chemicals should be followed.
|
| References | |
| Additional Infomation |
The 3-sulfate 4 and 3- and 17-glucuronide conjugates 5 and 6 of the pure anti-estrogenic steroid ICI 182,780 1 have been prepared, and this steroid is expected to become an effective drug for the treatment of breast cancer. The synthesis of compound 6 can only be successfully completed by reverse addition, a technique that has not been previously applied to the synthesis of glucuronic acid series compounds: this article discusses the value of this technique for the synthesis of some other aglycones. [1]
A3334 is also known as compound A3051 (CAS# 854171-31-6) with a molecular weight of 307.30 (C17H13N3O3). Its chemical name is 5'-methoxy-3-nitroso-1H,1'H-[2,3'-biindol]-2'-ol. It is a preclinical research tool derived from patent WO2020079569 and is not approved for clinical use. It is stored as a powder at -20degC and is stable for up to 3 years. |
| Molecular Formula |
C38H55F5O9S
|
|---|---|
| Molecular Weight |
782.8949
|
| Exact Mass |
782.348
|
| CAS # |
261506-27-8
|
| PubChem CID |
11072768
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
863.2±65.0 °C at 760 mmHg
|
| Flash Point |
475.8±34.3 °C
|
| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.552
|
| LogP |
5.61
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
53
|
| Complexity |
1230
|
| Defined Atom Stereocenter Count |
11
|
| SMILES |
C[C@@]12[C@@H](O)CC[C@H]1[C@@H]1[C@H](CCCCCCCCCS(CCCC(C(F)(F)F)(F)F)=O)CC3C([C@H]1CC2)=CC=C(O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(=O)O)O1)C=3
|
| InChi Key |
RSOPWVCNVAHMQZ-HMGPPUQISA-N
|
| InChi Code |
InChI=1S/C38H55F5O9S/c1-36-17-15-26-25-12-11-24(51-35-32(47)30(45)31(46)33(52-35)34(48)49)21-23(25)20-22(29(26)27(36)13-14-28(36)44)10-7-5-3-2-4-6-8-18-53(50)19-9-16-37(39,40)38(41,42)43/h11-12,21-22,26-33,35,44-47H,2-10,13-20H2,1H3,(H,48,49)/t22-,26-,27+,28+,29-,30+,31+,32-,33+,35-,36+,53?/m1/s1
|
| Chemical Name |
(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[[(7R,8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl]oxy]oxane-2-carboxylic acid
|
| Synonyms |
Fulvestrant 3-; A-D-Glucuronide; 261506-27-8; Fulvestrant 3-beta-D-glucuronide; RB33MP5RCR; Fulvestrant 3-b-D-Glucuronide; UNII-RB33MP5RCR; (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[[(7R,8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-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
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|---|---|
| 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 | 1.2773 mL | 6.3866 mL | 12.7732 mL | |
| 5 mM | 0.2555 mL | 1.2773 mL | 2.5546 mL | |
| 10 mM | 0.1277 mL | 0.6387 mL | 1.2773 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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