| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
FXR DUBTAC IN-1 (compound D11) (1-10 μM; 24 h) significantly increased the expression of FXR protein in HepG2 cells while maintaining 70.71% cell viability at a concentration of 50 μM [1]. FXR DUBTAC IN-1 (0.1-10 μM) dose-dependently increased the level of FXR protein in HepG2 cells [1]. FXR DUBTAC IN-1 (1 μM; 1-8 h) time-dependently increased the level of FXR protein in HepG2 cells, with a significant increase detectable from 1 h and lasting until 8 h [1]. FXR DUBTAC IN-1 stabilized FXR protein by promoting deubiquitination of FXR protein in HepG2 cells, which was manifested by decreased FXR polyubiquitination level and increased FXR protein level after treatment [1]. FXR DUBTAC IN-1 binds to purified FXR protein with a dissociation constant (Kd) of 2.12 × 10⁻⁵ M, as determined by surface plasmon resonance [1]. The stabilizing effect of FXR DUBTAC IN-1 on FXR protein is dependent on OTUB1 in HepG2 cells, as knockdown of OTUB1 eliminates the FXR stabilizing effect induced by FXR DUBTAC IN-1 [1]. FXR DUBTAC IN-1 (2 μM; duration of action up to 120 min) exhibits good metabolic stability in mouse and rat liver microsomes, with half-lives exceeding 120 min in both species [1].
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|---|---|
| ln Vivo |
FXR DUBTAC IN-1 (compound D11) (1–2.5 mg/kg; intraperitoneal injection; once daily for 5 days) stabilizes hepatic FXR protein and exerts a potent dose-dependent hepatoprotective effect against ANIT-induced cholestasis, with efficacy comparable to or better than equivalent or lower doses of obeticholic acid (OCA) [1]. FXR DUBTAC IN-1 (1–2.5 mg/kg; intraperitoneal injection; once daily for 3 days) alleviates cholestatic liver injury in an OTUB1-dependent manner, as knockdown of OTUB1 completely eliminates its hepatoprotective effect [1].
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| Cell Assay |
Western Blot Analysis [1]
Cell Types: HepG2 cells Tested Concentrations: 1 μM, 10 μM, 50 μM Incubation Duration: 24 hours (1 μM, 10 μM); unspecified time (50 μM) Experimental Results: FXR protein expression was significantly increased at 1 μM concentration, and further increased at 10 μM concentration. Cell viability remained at 70.71% at 50 μM concentration. Western Blot Analysis [1] Cell Types: HepG2 cells Tested Concentrations: 1 μM Incubation Duration: 1 hour, 2 hours, 4 hours, 8 hours Experimental Results: FXR protein was induced to stabilize in a time-dependent manner, and the FXR protein level began to increase after 1 hour of incubation. |
| Animal Protocol |
Animal/Disease Models:C57BL/6J (male, 6 weeks old, 20 g, ANIT-induced cholestasis) [1]
Doses: 1 mg/kg; 2.5 mg/kg Route of Administration: Intraperitoneal injection; once daily for 5 consecutive days Experimental Results: Significantly increased the level of FXR protein in the liver of mice with ANIT-induced cholestasis. Significantly reduced serum ALT, AST, ALP and TBA levels in a dose-dependent manner. At a dose of 1 mg/kg, its efficacy was comparable to that of obeticholic acid (OCA) at a dose of 2.5 mg/kg, and it was superior to OCA in reducing transaminases. Hematoxylin-eosin (H&E) staining showed histological improvement in the liver. Animal/Disease Models:C57BL/6J (male, 6 weeks old, cholestasis induced by ANIT-induced OTUB1 knockdown via AAV8-shRNA) [1] Doses: 1 mg/kg; 2.5 mg/kg Route of Administration: Intraperitoneal injection; once daily for 3 consecutive days Experimental Results: Reversed ANIT-induced downregulation of liver FXR protein, significantly reduced serum ALT, AST, ALP and TBA levels, and improved liver histology in control shRNA-injected mice. Failed to restore liver FXR protein levels in OTUB1-knockdown mice, failed to reduce serum cholestasis markers, and failed to improve liver histology. |
| References |
| Molecular Formula |
C43H66N4O7
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|---|---|
| Molecular Weight |
751.01
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| CAS # |
3081876-96-9
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
O[C@@H]1CC[C@@]2([C@]3(CC[C@@]4([C@@](CC[C@]4([C@@]3([C@@H](C([C@]2([H])C1)CC)O)[H])[H])([H])[C@@H](CCC(NCCCNC(CCC5=CC=C(N6C(CN(CC6)C(C=C)=O)=O)O5)=O)=O)C)C)[H])C
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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) |
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 | 1.3315 mL | 6.6577 mL | 13.3154 mL | |
| 5 mM | 0.2663 mL | 1.3315 mL | 2.6631 mL | |
| 10 mM | 0.1332 mL | 0.6658 mL | 1.3315 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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