Imeglimin hydrochloride
(Synonyms: (6R)-1,6-二氢-N2,N2,6-三甲基-1,3,5-三嗪-2,4-二胺盐酸盐,EMD 387008 hydrochloride) 目录号 : GC10956
Imeglimin hydrochloride是一种口服降糖药物，可抑制多药及毒素外排蛋白1（MATE1），IC50值为19.24μM。
Cas No.:775351-61-6
Sample solution is provided at 25 µL, 10mM.
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Imeglimin hydrochloride is an oral glucose-lowering agents, inhibiting Multidrug and toxin extrusion protein 1 (MATE1) with an IC50 value of 19.24μM[1]. Imeglimin hydrochloride has been widely used in anti-diabetes research and mitochondrial function research[2].
In vitro, Imeglimin hydrochloride (10mM; 4 hours) treatment can prevent cell death of HMEC-1 cells caused by tBH and hyperglycemia, and block the release of cytochrome c[3]. The human hepatoma cell line HepG2 was treated with Imeglimin hydrochloride at a concentration of 10mM for 3 hours, resulting in a significant decrease in the oxygen consumption rate (OCR) under the basal state, along with a significant decrease in ATP production[4]. When treated at a concentration of 1mM for 48 hours, Imeglimin hydrochloride significantly weakened the activity of mitochondrial complex I in 3T3-L1 adipocytes and promoted the synthesis and secretion of mitochondrial factors in adipocytes[5].
In vivo, Imeglimin hydrochloride treatment through oral gavage at a dose of 50mg/kg/day for 9 weeks reduced the area of atherosclerotic plaques, decreased fasting blood glucose and low-density lipoprotein cholesterol levels in diabetic ApoE-/- mice[6]. Oral administration of Imeglimin hydrochloride at a dose of 200mg/kg twice a day for 60 days can protect mitochondrial function from oxidative stress and promote lipid oxidation in the liver of high-fat and high-sugar diet (HFHSD) mouse models, restoring normal glucose tolerance and insulin sensitivity[7].
References:
[1]Clémence C, Fouqueray P, Sébastien B. In vitro investigation, pharmacokinetics, and disposition of imeglimin, a novel oral antidiabetic drug, in preclinical species and humans[J]. Drug Metabolism and Disposition, 2020, 48(12): 1330-1346.
[2]Chevalier C, Perrimond-Dauchy S, Dubourg J, et al. Lack of drug–drug interaction between cimetidine, a renal transporter inhibitor, and imeglimin, a novel oral antidiabetic drug, in healthy volunteers[J]. European Journal of Drug Metabolism and Pharmacokinetics, 2020, 45: 725-733.
[3]Detaille D, Vial G, Borel A L, et al. Imeglimin prevents human endothelial cell death by inhibiting mitochondrial permeability transition without inhibiting mitochondrial respiration[J]. Cell death discovery, 2016, 2(1): 1-8.
[4]Hozumi K, Sugawara K, Ishihara T, et al. Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes[J]. Scientific Reports, 2023, 13(1): 746.
[5]Takahashi N, Kimura A P, Yoshizaki T, et al. Imeglimin modulates mitochondria biology and facilitates mitokine secretion in 3T3-L1 adipocytes[J]. Life Sciences, 2024, 349: 122735.
[6]Lee J Y, Kang Y, Jeon J Y, et al. Imeglimin Inhibits Macrophage Foam Cell Formation and Atherosclerosis in Streptozotocin-Induced Diabetic ApoE-Deficient Mice[J]. Cells, 2025, 14(7): 472.
[7]Vial G, Chauvin M A, Bendridi N, et al. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model[J]. Diabetes, 2015, 64(6): 2254-2264.
Imeglimin hydrochloride是一种口服降糖药物，可抑制多药及毒素外排蛋白1（MATE1），IC50值为19.24μM[1]。Imeglimin hydrochloride在抗糖尿病研究和线粒体功能研究中具有广泛应用价值[2]。
在体外，当使用10mM浓度的Imeglimin hydrochloride处理HMEC-1细胞4小时后，能够有效阻止叔丁基过氧化氢（tBH）和高糖诱导的细胞死亡，并阻断细胞色素c的释放[3]。在人肝癌细胞系HepG2中，10mM浓度的Imeglimin hydrochloride处理3小时可显著降低基础状态下的氧消耗速率（OCR），同时减少ATP生成[4]。在3T3-L1脂肪细胞中，1mM浓度的Imeglimin hydrochloride处理48小时能明显减弱线粒体复合物I的活性，并促进脂肪细胞中多种线粒体因子的合成与分泌[5]。
在体内，糖尿病ApoE-/-小鼠模型经50mg/kg/day剂量的Imeglimin hydrochloride口服灌胃治疗9周后，动脉粥样硬化斑块面积显著缩小，空腹血糖和低密度脂蛋白胆固醇水平明显降低[6]。在高脂高糖饮食（HFHSD）小鼠模型中，每日两次、每次200mg/kg剂量的Imeglimin hydrochloride连续给药60天，可保护肝脏线粒体功能免受氧化应激损伤，促进肝脏脂质氧化代谢，使葡萄糖耐量和胰岛素敏感性恢复正常水平[7]。
| Cell experiment [1]: | |
Cell lines | HMEC-1 46 cells |
Preparation Method | The immortalized human dermal microvascular endothelial cell line HMEC-1 46 was cultured in MCDB-131 medium until conformance. 15% heat-inactivated fetal bovine serum (FBS), 2mM L-glutamine, 50UI/ml penicillin, 50μg/ml streptomycin, 10ng/ml epidermal growth factor and 1μg/ml hydrocortisone were added to the culture medium and cultured in a moist environment at 37°C (5%CO2). HMEC-1 was pre-incubated with Imeglimin hydrochloride (10 and 100mM; 4h) or CsA (1μM for 30 minutes), washed with PBS, and then exposed to 0.5mM tert-butylhydroperoxide (tBH) in FBS-free medium for 45 minutes. Then the cells were washed with PBS and incubated in complete MCDB medium at 37°C for 24 hours. Alternatively, the cells were exposed to 5.5mM glucose (control cells) or 33mM glucose for 48 hours. Cytotoxicity was evaluated using the Annexin V-Fluoprobes 488 kit combined with the double staining system of propidium iodide. Data acquisition was performed using a flow cytometer equipped with a 15mW argon ion laser (tuned to 488nm). |
Reaction Conditions | 10 and 100mM; 4h |
Applications | Imeglimin hydrochloride can prevent cell death induced by tBH or hyperglycemia. |
| Animal experiment [2]: | |
Animal models | Zucker diabetic fatty (ZDF) male rats |
Preparation Method | The experimental subjects were seven-week-old male ZDF rats. Before the experiment begins, the animals need to adapt to the breeding environment and undergo a one-week training in drug administration and operation. The animals were raised in a room with constant temperature and humidity (50 ± 20%), and a 12-hour day-night cycle was set up (with lights on at 7:00 a.m.). All rats could consume the common growth feed A03 and drink water freely. The rats were divided into groups of 3 to 4 rats per cage. The cage size is 48×37.5×21 centimeters. Observe the general signs of rats. Only animals without any abnormal signs were included in the study. The first group of animals, a total of 32 rats, were given Imeglimin hydrochloride by gavage for 5 consecutive weeks starting from 7 weeks of age at a dose of 150mg/kg twice a day, or given a carrier (0.5% methylcellulose). Body weight was monitored on the 1st, 4th, 8th, 11th, 15th, 18th, 22nd, 25th, 29th, 32nd, 36th and 38th days after the first day of administration. After 5 weeks of treatment, an oral glucose tolerance test (OGTT) was performed on rats that were fasted for 3 hours after being given a vector or Imeglimin hydrochloride for 1 hour in the morning. The first blood sample was collected at T0 before oral glucose loading (5mL/kg), and other blood samples were collected at T+10, T+20, T+30, T+60 and T+120 minutes after glucose loading. All plasma samples were frozen and stored at -20°C until blood glucose and insulin were measured. The total area (total AUC) and incremental AUC under the curve were calculated by using the trapezoidal method. In the second group of animals, a total of 8 rats received intragastric administration of Imeglimin hydrochloride at a dose of 150mg/kg twice daily or in combination with the excipient (methylcellulose). Five weeks later, the animals were euthanized, the tissues were taken and analyzed. |
Dosage form | 150mg/kg/twice a day for 5 weeks; p.o. |
Applications | In male ZDF rats, Imeglimin hydrochloride treatment significantly improved glucose-stimulated insulin secretion (increased the insulin production index) and improved blood glucose levels. |
References: | |
| Cas No. | 775351-61-6 | SDF | |
| 别名 | (6R)-1,6-二氢-N2,N2,6-三甲基-1,3,5-三嗪-2,4-二胺盐酸盐,EMD 387008 hydrochloride | ||
| 化学名 | (R)-6-imino-N,N,4-trimethyl-1,4,5,6-tetrahydro-1,3,5-triazin-2-amine hydrochloride | ||
| Canonical SMILES | C[C@](N=C(N(C)C)N1)([H])NC1=N.Cl | ||
| 分子式 | C6H14ClN5 | 分子量 | 191.66 |
| 溶解度 | ≥ 29.9mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.2176 mL | 26.0879 mL | 52.1757 mL |
| 5 mM | 1.0435 mL | 5.2176 mL | 10.4351 mL |
| 10 mM | 0.5218 mL | 2.6088 mL | 5.2176 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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