MB05032 |
| Catalog No.GC12084 |
An inhibitor of FBPase
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 261365-11-1
Sample solution is provided at 25 µL, 10mM.
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MB05032 is a potent and selective GNG inhibitor targeted the AMP binding site of fructose 1,6-bisphosphatase (FBPase) with an IC50 value of 16 nM [1].Gluconeogenesis (GNG) is a metabolic pathway which could result in the generation of glucose from certain non-carbohydratecarbon substrates.
In vitro: MB06322 inhibited glucose synthesis by human hepatocytes over a narrow concentration range with full inhibition achieved at 1 μM in a concentration-dependent manner [2]. MB05032 inhibited human liver FBPase with a potency (IC50 of 16 ± 1.5 nM) significantly greater than the natural inhibitor, AMP (IC50 of 1 μM), and the most well characterized AMP mimetic, ZMP (IC50of 12 ± 1.4 μM). MB05032 inhibited rat FBPase 3-fold weaker (IC50 of 61 ± 4 nM) than human FBPase, whereas AMP was 20-fold weaker as an inhibitor [1]. In islet β-cells,inhibition of FBPase activity by MB05032 led to a significant increase of their glucose utilization and cellular ATP to ADP ratios and consequently enhanced GSIS in vitro [2].
In vivo: In male ZDF rats, oral administration of MB06322 resulted in dose-dependent inhibition of [14C]bicarbonate incorporation into glucose. Maximal GNG inhibition (≈80%) is achieved at 100–300 mg/kg MB06322. In MB06322-treated rats, intermediates upstream of FBPase WERE elevated 1.5- to 3.1-fold relative to vehicle-treated mice. MB06322 treatment also resulted in elevated lactate levels (79%) only in aged ZDF rats. [2]. Oral administration of MB06322 to young (8–9 weeks old) ZDF rats with mild diabetes (basal insulin levels of 7.7 ± 0.7 ng/ml) and aged (12–13 weeks) ZDF rats with overt diabetes (basal insulin levels of 0.65 ± 0.16 ng/ml) lowered the level of glucose in a dose-dependent manner [1]. The dose–dependent response is relatively steep, with 6–10 mg/kg and 30–100 mg/kg being the approximate doses associated with minimal and maximal activity, respectively. After drug administration 2.5–5 h, glucose lowering occurs rapidly with maximal effects [1].
References:
[1] Erion M D, van Poelje P D, Dang Q, et al. MB06322 (CS-917): A potent and selective inhibitor of fructose 1, 6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes[J]. Proceedings of the National Academy of Sciences, 2005, 102(22): 7970-7975.
[2] Zhang Y, Xie Z, Zhou G, et al. Fructose-1, 6-bisphosphatase regulates glucose-stimulated insulin secretion of mouse pancreatic β-cells[J]. Endocrinology, 2010, 151(10): 4688-4695.
| Kinase experiment [1]: | |
|
Binding assays |
Fructose 1,6-bisphosphatase (FBPase) activity was measured spectrophotometrically in reactions that coupled the production of fructose 6-phosphate to the reduction of NADP+. AMP-activated protein kinase (rat liver) was assayed by using the peptide substrate SAMS according to the supplier’s instructions. AMP deaminase (porcine heart) was purified and assayed as described in ref. 21. Glycogen phosphorylase (rabbit muscle), phosphofructokinase (rabbit liver), and adenylate kinase (rabbit muscle) were assayed as described in refs. Kinetic parameters were calculated by means of four-parameter logistics regression with use of SIGMAPLOT 2000 software. |
| Cell experiment [1]: | |
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Cell lines |
rat and human hepatocytes |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0.001-100 μM; 15-30 min |
|
Applications |
In rat and human hepatocytes, MB05032 concentration-dependently inhibited glucose production from all common GNG precursors. Relative to MB06322, MB05032 was a 5- and 226-fold less potent inhibitor of glucose synthesis by rat and human hepatocytes, respectively. |
|
References: [1] Erion M D, van Poelje P D, Dang Q, et al. MB06322 (CS-917): A potent and selective inhibitor of fructose 1, 6-bisphosphatase for controlling gluconeogenesis in type 2 diabetes[J]. Proceedings of the National Academy of Sciences, 2005, 102(22): 7970-7975. | |
| Cas No. | 261365-11-1 | SDF | |
| Chemical Name | (5-(2-amino-5-isobutylthiazol-4-yl)furan-2-yl)phosphonic acid | ||
| Canonical SMILES | NC1=NC(C2=CC=C(P(O)(O)=O)O2)=C(CC(C)C)S1 | ||
| Formula | C11H15N2O4PS | M.Wt | 302.29 |
| Solubility | DMSO : 50 mg/mL (165.40 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3081 mL | 16.5404 mL | 33.0808 mL |
| 5 mM | 0.6616 mL | 3.3081 mL | 6.6162 mL |
| 10 mM | 0.3308 mL | 1.654 mL | 3.3081 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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