Imeglimin-hydrochloride-EMD-387008-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEImeglimin hydrochlorideCat. No.: HY-14771ACAS No.: 775351-61-6Synonyms: EMD 387008 hydrochloride分式: CHClN分量: 191.66作靶點(diǎn): Mitochondrial Metabolism作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 mo

2、nths-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 25 mg/mL (130.44 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 5.2176 mL 26.0879 mL 52.1757 mL5 mM 1.0435 mL 5.2176 mL 10.4351 mL10 mM 0.5218 mL 2.6088 mL 5.2176 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄

3、清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (13.04 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (13.04 mM); Clear solution3. 請(qǐng)依序

4、添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (13.04 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Imeglimin hydrochloride第個(gè)誘導(dǎo)線粒體磷脂 (mitochondrial phospholipid) 成分增加的抗糖尿病化合物，有助于改善肝臟線粒體功能。IC50 & Target Mitochondrial phospholipid 1體外研究 Imeglimin also r

5、educes reactive oxygen species production and increases mitochondrial DNA. Imeglimineffects on mitochondrial phospholipid composition can participate in the benefit of Imeglimin on mitochondrialfunction. Imeglimin increases mtDNA content without modifying PGC1 expression. Imeglimin amplifies theeffe

6、cts of high-fat, high-sucrose diet (HFHSD) on both cardiolipin and phosphatidylserine (PS) content,whereas it tends to restore phosphatidylcholine (PC), phosphatidylethanolamine (PE), andphosphatidylinositol (PI) content to normal values in HFHSD mitochondria 1.體內(nèi)研究 Imeglimin is administered orally

7、at 200 mg/kg b.i.d. during the last 6 weeks of the HFHSD feeding protocol. Aslight decrease in body weight and food intake associated with some diarrhea is observed but only during thefirst few days of treatment. Imeglimin significantly decreases hyperglycemia, restores normal glucosetolerance, and

8、improves insulin sensitivity 1.PROTOCOLKinase Assay 1 Rotenone-sensitive NADH-ubiquinone oxidoreductase (complex I, CI) is assayed using 100 MDecylubiquinone as an electron acceptor and 200 M NADH as a donor in a 10 mM KH2PO4/K2HPO4buffer, pH 7.5, containing 3.75 mg/mL BSA, 2 mM KCN, and 7.5 M Antim

9、ycin A. NADH oxidation ismeasured at 340 nm before and after the addition of 4 M Rotenone to allow the calculation of the Rotenone-sensitive-specific activity, which is characteristic of CI. Succinate-ubiquinone reductase (complex II, CII)activity is quantified by measuring the decrease in absorbanc

10、e resulting from the reduction of 100 Mdichlorophenolindophenol at 600 nm. The measurement is performed in 50 mM KH2PO4/K2HPO4 buffer, pH7.5, in the presence of 30 mM Succinate, 100 M Decylubiquinone, 2 M Rotenone, and 2 mM KCN.Coenzyme Q-cytochrome c-oxidoreductase activity (complex III, CIII), is

11、quantified by measuring theincrease in absorbance resulting from the reduction of 100 M cytochrome c at 550 nm. The measurement isperformed in 50 mM KH2PO4/K2HPO4 buffer, pH 7.5, in the presence of 100 M Decylubiquinone previouslyreduced by dithionite, 50 M EDTA, and 1 mM KCN. The specific activity

12、is calculated by subtracting theactivity obtained before and after addition of 5 g/mL Antimycin A. 3-Hydroxyacyl-CoA dehydrogenase (HAD)activity is quantified by measuring the decrease in absorbance at 340 nm resulting from the oxidation ofNADH (200 M) and the reduction of S-acetoacetyl-CoA (50 M).

13、The measurement is performed inImidazole (40 mM) and EDTA (60 M), pH 7 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 12/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAdministration 1 Male C57BL/6JOlaHsd mice at 4 weeks old are housed at

14、 22C with a 12-h light/dark cycle. After 1 week ofacclimatization, 5-6-week-old mice are divided into two groups: one with free access to a standard chow diet(SD) and the other with free access to a pelleted HFHSD diet for 16 weeks. Animals receive Imeglimin 200mg/kg b.i.d. by oral gavage during the

15、 last 6 weeks of HFHSD feeding. Control SD and HFHSD mice aretreated by oral gavage with methylcellulose 0.5% as a vehicle for drug treatment (5 mL/kg). Food intake ismeasured every day during the first week and twice a week until the end of the experiment. Results areexpressed as grams per day per mouse.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Vial G, et al. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrialfunction in liver of a high-fat,high-sucrose diet mice m