| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
Imeglimin targets mitochondrial bioenergetics to ameliorate insulin resistance and enhance β-cell function. It is a small cationic drug with a complex mechanism of absorption involving active transport through organic cation transporters (OCTs). Imeglimin decreases ROS production by decreasing reverse electron transport at mitochondrial complex I. It prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration. Imeglimin also induces an increase in mitochondrial phospholipid composition.
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| ln Vitro |
Tert-butyl hydroperoxide (tBH)-induced cell death is totally prevented by preincubation with imeglimin (10 mM for 4 hours or 100 μM for 24 hours) [2].
In vitro, Imeglimin has been shown to improve mitochondrial function and reduce ROS production. It prevents human endothelial cell death by inhibiting mitochondrial permeability transition. In a 24-week clinical trial comparing imeglimin (2000 mg/day) to metformin (1000 mg/day), imeglimin uniquely increased both total and active glucose-dependent insulinotropic polypeptide (GIP) levels, whereas metformin did not. These in vitro and clinical studies confirm Imeglimin's effects on mitochondrial function and glucose metabolism. |
| ln Vivo |
During the final six weeks of HFHSD feeding, meglimin (200 mg/kg b.i.d. oral) dramatically lowers hyperglycemia, returns normal glucose tolerance, and enhances insulin sensitivity [1].
In vivo, Imeglimin has been shown to decrease hyperglycemia, restore normal glucose tolerance, and improve insulin sensitivity in animal models. In clinical trials, Imeglimin has shown promise in helping to lower blood sugar levels without significant weight gain or hypoglycemia. A 24-week, open-label, randomized controlled trial compared imeglimin (2000 mg/day) to metformin (1000 mg/day) in patients with type 2 diabetes. Imeglimin is an investigational oral medication being studied for the treatment of type 2 diabetes. |
| Enzyme Assay |
In vitro enzyme assays for Imeglimin are not well-defined, as its mechanism of action is related to mitochondrial function rather than direct enzyme inhibition. Its effects on mitochondrial respiration can be measured using oxygen consumption assays. ROS production can be measured using fluorescent probes. The inhibition of mitochondrial permeability transition can be assessed using assays that measure mitochondrial swelling or membrane potential. These assays confirm the compound's effects on mitochondrial function.
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| Cell Assay |
Cell Viability Assay [2]
Cell Types: Human Endothelial Cells (HMEC-1) Tested Concentrations: 100 μM and 10 mM Incubation Duration: 100 μM 24 hrs (hours), 10 mM 4 hrs (hours) Experimental Results: Prevents cell death. In vitro cell-based assays for Imeglimin are used to study its effects on mitochondrial function and cell survival. Cells are treated with Imeglimin, and mitochondrial function is assessed by measuring oxygen consumption, ATP production, and ROS levels. Endothelial cell death is induced by various stimuli, and the protective effects of Imeglimin are assessed by measuring cell viability. These assays confirm the compound's cytoprotective and mitochondrial effects. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6JOlaHsd mice (4 weeks old) [1]
Doses: 200 mg/kg Route of Administration: po (oral gavage); bid; 6 weeks Experimental Results: A slight decrease in body weight and food intake was observed, and There is some diarrhea, but only during the first few days of treatment. In vivo animal experiments for Imeglimin have been conducted in animal models of diabetes. In a typical study, Imeglimin is administered orally to diabetic animals, and blood glucose levels, insulin sensitivity, and glucose tolerance are measured. Mitochondrial function in liver and muscle tissues is assessed. These studies confirm the in vivo efficacy of Imeglimin in improving glucose metabolism and mitochondrial function. |
| ADME/Pharmacokinetics |
Imeglimin has a molecular weight not specified in standard product descriptions. It is a solid compound. It is soluble in DMSO and other organic solvents. For storage, it is recommended to keep the powder at -20°C. Pharmacokinetic properties have been characterized in clinical studies. Imeglimin is absorbed through organic cation transporters (OCTs). Detailed pharmacokinetic parameters, such as half-life and bioavailability, are available from clinical trial data.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for Imeglimin is available from its clinical development. In clinical trials, Imeglimin has been shown to be generally well-tolerated. Common side effects may include gastrointestinal disturbances. However, specific toxicity data, such as adverse effects or organ toxicity, are not detailed in standard product descriptions. As with all research chemicals, standard laboratory safety precautions should be followed when handling Imeglimin.
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| References |
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| Additional Infomation |
Imeglimin has been used in trials investigating the treatment of type 2 diabetes.
Imeglimin (EMD 387008) is an investigational oral medication being studied for the treatment of type 2 diabetes. It is the first in a tetrahydrotriazine-containing class of oral antidiabetic agents, the glimins. Imeglimin improves insulin sensitivity and reduces reactive oxygen species (ROS) production. It increases mitochondrial DNA and improves mitochondrial function. Imeglimin acts on the liver, muscle, and pancreatic β-cells to target the key defects of type 2 diabetes. It has shown promise in clinical trials. |
| Exact Mass |
155.117
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|---|---|
| CAS # |
775351-65-0
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| Related CAS # |
Imeglimin hydrochloride;775351-61-6
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| PubChem CID |
24812808
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| Appearance |
White to off-white solid
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| LogP |
-1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
11
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| Complexity |
205
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H]1N=C(NC(=N1)N(C)C)N
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| InChi Key |
GFICWFZTBXUVIG-SCSAIBSYSA-N
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| InChi Code |
InChI=1S/C6H13N5/c1-4-8-5(7)10-6(9-4)11(2)3/h4H,1-3H3,(H3,7,8,9,10)/t4-/m1/s1
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| Chemical Name |
(4R)-6-N,6-N,4-trimethyl-1,4-dihydro-1,3,5-triazine-2,6-diamine
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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: ~32 mg/mL (~206.2 mM; with ultrasonication and warming by heating to 60°C)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.2 mg/mL (20.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (32.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 3.2 mg/mL (20.62 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 DMSO stock solution (32.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
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.
Imeglimin add-on therapy:A randomized, double-blind, clinical trial
CTID: jRCTs061210082
Phase: Status: Recruiting
Date: 2022-03-04
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