MK 0893 |
| Catalog No.GC14793 |
MK 0893 is a potent and selective glucagon receptor (GCGR) antagonist with an IC50 value of 6.6 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 870823-12-4
Sample solution is provided at 25 µL, 10mM.
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MK 0893 is a potent and selective glucagon receptor (GCGR) antagonist with an IC50 value of 6.6 nM[1]. The mechanism of action of MK 0893 is to prevent GCGR activation by limiting the movement of transmembrane helix 6 (TM6) protein required for G protein signaling [2]. MK-0893 treats patients with type 2 diabetes and effectively reduces postprandial blood sugar, but it will cause an increase in liver transaminases and is not suitable for clinical development [3].
In vitro, MK 0893 (0-1000nM) treated human primary liver cells for 1 hour, inhibited the effect of glucagon and prevented it from inducing the production of cAMP, with an IC50 value of 563nM [4]. MK 0893 (0-400nM) treated INS-1 832/13 cells and inhibited the effects of glucagon and also inhibited the effects of glucagon-like peptide-1 (GLP-1) [5].
In vivo, oral administration of MK 0893 (3, 10 mg/kg) to hGCGR ob/ob mice reduced blood glucose levels by 32% and 39% at single doses of 3 and 10 mg/kg, respectively [1]. MK 0893 (3, 10 mg/kg) administered orally to WT and hGCGR mice did not significantly affect plasma cholesterol or plant sterol levels in WT mice, however, at a dose of 10 mg/kg, it significantly increased campesterol levels. In hGCGR mice, MK 0893 exhibited a dose-dependent increase in plasma sitosterol levels [4].
References:
[1] Xiong Y, Guo J, Candelore M R, et al. Discovery of a Novel Glucagon Receptor AntagonistN-[(4-{(1S)-1-[3-(3, 5-Dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1 H-pyrazol-1-yl] ethyl} phenyl) carbonyl]-β-alanine (MK-0893) for the Treatment of Type II Diabetes[J]. Journal of medicinal chemistry, 2012, 55(13): 6137-6148.
[2] Crunkhorn S. Glucagon receptor antagonist binding site identified[J]. Nature Reviews Drug Discovery, 2016, 15(6): 384-384.
[3] Christensen M, Bagger J I, Vilsboll T, et al. The alpha-cell as target for type 2 diabetes therapy[J]. The review of diabetic studies: RDS, 2011, 8(3): 369.
[4] Guan H P, Yang X, Lu K, et al. Glucagon receptor antagonism induces increased cholesterol absorption [S][J]. Journal of lipid research, 2015, 56(11): 2183-2195.
[5] Chepurny O G, Matsoukas M T, Liapakis G, et al. Nonconventional glucagon and GLP-1 receptor agonist and antagonist interplay at the GLP-1 receptor revealed in high-throughput FRET assays for cAMP[J]. Journal of Biological Chemistry, 2019, 294(10): 3514-3531.
Cell experiment [1]: | |
Cell lines | Human primary hepatocytes |
Preparation method | 4,000 cells per well were preincubated with MK-0893, GRA1, and GRA2 (0-1000nM) for 30 min and restimulated with glucagon (5nM) for 30 min at room temperature. |
Reaction Conditions | 0-1000nM; 1 h |
Applications | In the presence of glucagon, MK-0893, GRA1, and GRA2 all inhibit cAMP production with IC50 of 563, 448, and 292 nM, respectively. |
Animal experiment [2]: | |
Animal models | hGCGR ob/ob mice |
Preparation method | hGCGR ob/ob mice at 1 h post MK 0893 (3, 10mg/kg) administration via po, glucagon dissolved in PBS was injected at 15μg/kg ip followed by glucose measurements using a glucometer via tail bleeding. |
Dosage form | 3, 10mg/kg; p.o. |
Applications | MK 0893 at 10 and 3 mg/kg oral doses lowered blood glucose level by 39%, 32% respectively. |
References: [1] Guan H P, Yang X, Lu K, et al. Glucagon receptor antagonism induces increased cholesterol absorption [S][J]. Journal of lipid research, 2015, 56(11): 2183-2195. [2] Xiong Y, Guo J, Candelore M R, et al. Discovery of a Novel Glucagon ReceptorAntagonistN-[(4-{(1S)-1-[3-(3,5-Dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1 H-pyrazol-1-yl] ethyl} phenyl) carbonyl]-β-alanine (MK-0893) for the Treatment of Type II Diabetes[J]. Journal of medicinal chemistry, 2012, 55(13): 6137-6148. | |
| Cas No. | 870823-12-4 | SDF | |
| Chemical Name | 3-[[4-[(1S)-1-[3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)pyrazol-1-yl]ethyl]benzoyl]amino]propanoic acid | ||
| Canonical SMILES | CC(C1=CC=C(C=C1)C(=O)NCCC(=O)O)N2C(=CC(=N2)C3=CC(=CC(=C3)Cl)Cl)C4=CC5=C(C=C4)C=C(C=C5)OC | ||
| Formula | C32H27Cl2N3O4 | M.Wt | 588.48 |
| Solubility | ≥ 24.05 mg/mL in DMSO, ≥ 4.8 mg/mL in EtOH with ultrasonic and warming | 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 | 1.6993 mL | 8.4965 mL | 16.9929 mL |
| 5 mM | 0.3399 mL | 1.6993 mL | 3.3986 mL |
| 10 mM | 0.1699 mL | 0.8496 mL | 1.6993 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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
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- Purity: >99.00%
- 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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