| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Glucokinase (GK). AM-2394 functions as a potent and selective allosteric activator of glucokinase, the enzyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate. It binds to an allosteric site on glucokinase, increasing the enzyme's affinity for glucose by approximately 10-fold. This sensitizes the enzyme to ambient glucose levels, leading to enhanced glucose metabolism. In pancreatic β-cells, GK activation leads to increased glycolysis, a higher ATP:ADP ratio, closure of ATP-sensitive potassium channels, membrane depolarization, and subsequent insulin secretion. In hepatocytes, GK activation promotes hepatic glucose uptake and the conversion of glucose into glycogen for storage.
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| ln Vitro |
AM-2394 demonstrates potent glucokinase activation in vitro, with an EC50 of 60 nM. In enzyme assays performed in the presence of glucose, it increases the affinity of GK for glucose by approximately 10-fold. The compound exhibits a Vmax of 1.2 relative to the unactivated enzyme and a substrate concentration (S0.5) of 0.73 mM for glucose in the presence of AM-2394. Its in vitro potency and selectivity have been characterized in enzymatic assays.
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| ln Vivo |
AM-2394 is a physically unique glucokinase activator that dramatically decreases plasma glucose at a dose of 3 mg/kg in the oral glucose tolerance test (OGTT) in ob/ob mice. AM-2394 improves the affinity of glucokinase (GK) for glucose by about 10-fold, demonstrates moderate clearance and acceptable oral bioavailability in numerous animal models, and is fed orally in a diabetic ob/ob mice model Reduce glucose excursions during glucose tolerance tests. AM-2394 displays good to moderate plasma clearance, volume of distribution and oral bioavailability across species and can be further studied in animal models [1].
In vivo, AM-2394 has been shown to produce a robust, dose-dependent reduction in plasma glucose in animal models of diabetes. In an oral glucose tolerance test (OGTT) using ob/ob mice, oral administration at doses of 1, 3, 10, and 30 mg/kg each reduced glucose excursion, with maximal efficacy observed at 3 mg/kg. The compound exhibits moderate clearance and good oral bioavailability across multiple animal models. |
| Enzyme Assay |
In vitro enzyme assays for AM-2394 typically involve measuring glucokinase activity in the presence of varying concentrations of the compound. Recombinant glucokinase is incubated with glucose, ATP, and a coupling enzyme system (e.g., glucose-6-phosphate dehydrogenase). The production of NADPH is monitored spectrophotometrically at 340 nm. AM-2394 is tested at concentrations ranging from sub-nanomolar to micromolar, and the EC50 value of 60 nM is determined from dose-response curves. The compound's ability to increase the affinity of GK for glucose is assessed by measuring the S0.5 value.
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| Cell Assay |
Cellular assays for AM-2394 are not typically performed as the compound acts directly on the glucokinase enzyme. However, the compound's effects on glucose metabolism can be assessed in cell-based systems such as primary hepatocytes or pancreatic β-cell lines. Cells are treated with AM-2394 at varying concentrations, and glucose uptake, glucose phosphorylation, or insulin secretion are measured. The compound's ability to enhance glucose-stimulated insulin secretion in β-cells or glycogen synthesis in hepatocytes can be evaluated.
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| Animal Protocol |
In vivo animal studies for AM-2394 have been conducted in mouse models of diabetes, particularly the ob/ob mouse model. The compound is typically administered orally (per os, PO) 30 minutes prior to performing an oral glucose tolerance test (OGTT). Doses of 1, 3, 10, and 30 mg/kg are commonly used. Blood glucose levels are measured at various time points after glucose challenge. Statistical significance compared to vehicle treatment is determined using two-way ANOVA. Terminal plasma exposure of AM-2394 is measured at 135 minutes post-OGTT.
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| ADME/Pharmacokinetics |
AM-2394 exhibits moderate clearance and good oral bioavailability across multiple animal species. In mice (1 mg/kg IV, 5 mg/kg PO), the oral Cmax is 0.35 μM, tmax is 0.33 h, clearance (Cl) is 0.37 L/h/kg, volume of distribution at steady state (Vdss) is 0.59 L/kg, IV half-life is 2.0 h, oral bioavailability (F) is 25%, and fraction unbound in plasma (Fub) is 0.13. In rats, the oral bioavailability is 60%. In cynomolgus monkeys, the oral bioavailability is 70%, and in dogs, it is 99%. The compound is soluble in DMSO (85 mg/mL) but insoluble in water.
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| Toxicity/Toxicokinetics |
As a glucokinase activator, AM-2394 carries the class-related risks of hypoglycemia caused by over-activation of glucokinase in islet cells and dyslipidemia caused by over-activation of intrahepatic glucokinase. Clinical studies with other GKAs have shown efficacy in glycemic control but a significant elevation in triglyceride (TG) concentration. Comprehensive toxicological data for AM-2394 are limited, and the compound is intended for research use only and is not approved for human therapeutic applications. Standard laboratory safety precautions should be taken when handling the compound.
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| References | |
| Additional Infomation |
AM-2394 is a potent, orally bioavailable, allosteric activator of glucokinase (GK) developed for the potential treatment of type 2 diabetes. It activates GK with an EC50 of 60 nM and increases the enzyme's affinity for glucose by approximately 10-fold. The compound demonstrates robust glucose-lowering efficacy in the oral glucose tolerance test in ob/ob mice at doses as low as 3 mg/kg. Its pharmacokinetic properties, including moderate clearance and good oral bioavailability, have been characterized in multiple species. AM-2394 was discovered through structure-activity relationship studies of benzamide derivatives as glucokinase activators. The compound is not approved for clinical use and is available only for research purposes.
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| Molecular Formula |
C22H25N5O4
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| Molecular Weight |
423.4650
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| Exact Mass |
423.19
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| CAS # |
1442684-77-6
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| Related CAS # |
1442684-77-6
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| PubChem CID |
71603585
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
578
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1C([H])=C([H])C(=C([H])N=1)C1=C([H])N=C(C([H])=C1OC1=C([H])N=C([H])C(C([H])([H])[H])=C1[H])N([H])C(N([H])C([H])([H])[H])=O)C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])O[H]
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| InChi Key |
QUISANLDBDCMPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H25N5O4/c1-14-7-16(11-24-9-14)31-18-8-19(27-21(28)23-4)25-12-17(18)15-5-6-20(26-10-15)30-13-22(2,3)29/h5-12,29H,13H2,1-4H3,(H2,23,25,27,28) SMILES
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| Chemical Name |
1-(6'-(2-hydroxy-2-methylpropoxy)-4-((5-methylpyridin-3-yl)oxy)-[3,3'-bipyridin]-6-yl)-3-methylurea
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| Synonyms |
AM-2394 AM 2394 AM2394.
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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) |
DMSO : ≥ 30 mg/mL (~70.84 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3614 mL | 11.8072 mL | 23.6144 mL | |
| 5 mM | 0.4723 mL | 2.3614 mL | 4.7229 mL | |
| 10 mM | 0.2361 mL | 1.1807 mL | 2.3614 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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