| Size | Price | Stock | Qty |
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| 10mg | |||
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| Targets |
AR453588 targets glucokinase (GK), a key enzyme in glucose metabolism that acts as a glucose sensor in pancreatic β-cells and the liver. As a glucokinase activator, it binds to an allosteric site on the enzyme, increasing its affinity for glucose and enhancing glucose phosphorylation. This leads to increased glucose uptake and utilization, improved insulin secretion, and reduced blood glucose levels. The compound has an EC50 of 42 nM.
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| ln Vitro |
In vitro studies have demonstrated that AR453588 is a potent glucokinase activator with an EC50 of 42 nM. It shows anti-hyperglycemic activity. As an orally bioavailable compound, it is suitable for in vitro characterization in enzyme assays using recombinant glucokinase. The compound's potency and oral bioavailability make it a valuable research tool for studying glucokinase activation and its effects on glucose metabolism. Further detailed in vitro characterization data are available from the compound's development.
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| ln Vivo |
In healthy C57BL/6J mice, AR453588 (3–30 mg/kg; oral) lowers postprandial blood glucose [1]. In ob/ob mice, AR453588 (3–30 mg/kg; oral; once daily for 14 days) showed anti-hyperglycemic activity over the course of the 14-day dose range [1]. Tmax, AUCinf, Vss, Cmax, and F of 1.0 mL/min/kg, 4.65 h μg/mL, 1.67 μg/mL, and 60.3%, respectively, were observed with AR453588 (10 mg/kg; po) treatment [1]. CL, AUCinf, Vss, and t1/2 of 21.6 mL/min/kg, 0.77 h μg/mL, 0.746 L/kg, and 1.28 h, respectively, were observed with AR453588 (1 mg/kg; iv) treatment [1].
In vivo studies have shown that AR453588 has anti-hyperglycemic activity. As an orally bioavailable glucokinase activator with an EC50 of 42 nM, it can be administered to animal models of type 2 diabetes to study its effects on blood glucose control. The compound shows strong potential in anti-diabetic research. It is used as a research tool for exploring type 2 diabetes and metabolic disease therapies. Detailed in vivo pharmacokinetic and efficacy studies are available from the compound's development. |
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for AR453588 typically involve glucokinase activation studies using recombinant human glucokinase. The enzyme is incubated with increasing concentrations of AR453588 (0.01 nM - 10 μM), glucose, and ATP in assay buffer at 37°C for 30-60 minutes. Glucose phosphorylation is measured by coupling the reaction to glucose-6-phosphate dehydrogenase and measuring NADPH production spectrophotometrically at 340 nm. EC50 values are calculated from dose-response curves by nonlinear regression. Enzyme kinetics can be analyzed to determine the mode of activation (e.g., changes in glucose affinity or Vmax). Selectivity for glucokinase over other hexokinases is assessed.
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| Cell Assay |
For in vitro cell-based assays, pancreatic β-cell lines (e.g., INS-1, MIN6) or hepatocytes are cultured in appropriate media. Cells are treated with AR453588 at concentrations ranging from 0.01 nM - 10 μM for 1-24 hours. Glucose-stimulated insulin secretion is measured by ELISA or radioimmunoassay. Glucose uptake is assessed using 2-deoxyglucose uptake assays. Cellular glucose metabolism is measured by assessing ATP levels or lactate production. Cell viability is assessed by MTT or CCK-8 assays. The compound's effects on glucokinase activity in cell lysates can be measured using enzymatic assays.
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| Animal Protocol |
Animal/Disease Models: Male diabetic ob/ob mice [1]
Doses: 3, 10, 30 mg/kg Route of Administration: Orally, one time/day for 14 days Experimental Results: diminished fasting blood glucose and AUC OGTT in control animals on day 14 (Oral Glucose Tolerance Test). Animal/Disease Models: Male CD-1 mice [1] Doses: 10 mg/kg Route of Administration: po (pharmacokinetic/PK/PK analysis) Experimental Results: Tmax, AUCinf, Vss, Cmax and F were 1.0 mL/min/kg, respectively. 4.65 h μg/mL, 1.67 μg/mL and 60.3% respectively. In vivo animal studies with AR453588 typically use rodent models of type 2 diabetes (e.g., db/db mice, ob/ob mice, or streptozotocin-induced diabetic rats). The compound is administered orally at doses determined from pharmacokinetic studies. Blood glucose levels are measured at various time points post-administration. Glucose tolerance tests are performed to assess glucose homeostasis. Insulin levels are measured by ELISA. Body weight and food intake are monitored. At study endpoint, blood samples are collected for pharmacokinetic analysis and measurement of HbA1c. Pancreatic and liver tissues are harvested for histopathological examination and biomarker analysis. |
| ADME/Pharmacokinetics |
AR453588 has a molecular weight of 519.64 g/mol and molecular formula C25H25N7O2S2. Chemical name: 1-{4-[5-({3-[(2-methylpyridin-3-yl)oxy]-5-(pyridin-2-ylsulfanyl)pyridin-2-yl}amino)-1,2,4-thiadiazol-3-yl]piperidin-1-yl}ethan-1-one. The compound is orally bioavailable. Pharmacokinetic parameters including oral bioavailability, Cmax, Tmax, AUC, and half-life are determined in preclinical species. The compound is intended for research purposes only.
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| Toxicity/Toxicokinetics |
In preclinical studies, AR453588 has shown a favorable safety profile at pharmacological doses. As a glucokinase activator, it is well-tolerated in animal models with no significant off-target toxicity reported at therapeutic doses. The compound's selectivity for glucokinase over other hexokinases reduces the risk of off-target effects. Standard toxicology studies including acute and subchronic toxicity assessments would be required for therapeutic development. The compound is intended for research purposes only and is not approved for human use.
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| References | |
| Additional Infomation |
AR453588 is a potent and orally bioavailable glucokinase activator (GKA) with anti-diabetic activity. It has an EC50 of 42 nM and shows anti-hyperglycemic activity. AR453588 has a molecular weight of 519.64 g/mol and molecular formula C25H25N7O2S2. It is used as a research tool for exploring type 2 diabetes and metabolic disease therapies. The compound is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C25H25N7O2S2
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| Molecular Weight |
519.6417
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| Exact Mass |
519.151
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| CAS # |
1065609-00-8
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| Related CAS # |
AR453588 hydrochloride;1065606-97-4
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| PubChem CID |
59291641
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
714
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(N([H])C2=C(C([H])=C(C([H])=N2)SC2=C([H])C([H])=C([H])C([H])=N2)OC2C([H])=C([H])C([H])=NC=2C([H])([H])[H])=NC(C2([H])C([H])([H])C([H])([H])N(C(C([H])([H])[H])=O)C([H])([H])C2([H])[H])=N1
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| InChi Key |
WITGITFYEMHCEZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H25N7O2S2/c1-16-20(6-5-11-26-16)34-21-14-19(35-22-7-3-4-10-27-22)15-28-24(21)30-25-29-23(31-36-25)18-8-12-32(13-9-18)17(2)33/h3-7,10-11,14-15,18H,8-9,12-13H2,1-2H3,(H,28,29,30,31)
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| Chemical Name |
1-[4-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone
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| Synonyms |
AR453588; AR-453588
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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 : ~100 mg/mL (~192.44 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.81 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 (4.81 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 (4.81 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 | 1.9244 mL | 9.6220 mL | 19.2441 mL | |
| 5 mM | 0.3849 mL | 1.9244 mL | 3.8488 mL | |
| 10 mM | 0.1924 mL | 0.9622 mL | 1.9244 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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