Dapagliflozin
(Synonyms: 达格列净; BMS-512148) 目录号 : GC15530
Dapagliflozin 是一种钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂，是一种新型抗糖尿病药物，由于其抑制 SGLT2 介导的肾葡萄糖重吸收的能力而被批准用于治疗 T2DM。
Cas No.:461432-26-8
Sample solution is provided at 25 µL, 10mM.
Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a novel antidiabetic agent that is approved for the treatment of T2DM by based on its ability to inhibit SGLT2-mediated renal glucose reabsorption. In addition to providing effective glycaemic control, dapagliflozin help decrease body weight, reduce rate of cardiovascular death, and possibly slow the progression of diabetic kidney diseases[1-3].
Dapagliflozin(20 µM;24h) promoted ACC1 phosphorylation and ACOX1 protein expression, promoted autophagy and alleviated lipid accumulation in PA-stimulated LO2 cells and HepG2 cells[4]. In diabetic proximal renal tubule cells, Dapaglide(20 µM;48h) net improved HG-induced autophagy flux reduction and inhibited mTOR by increasing AMPK activity, meanwhile dapagliflozin inhibited NF-κB pathway inflammatory changes[9].
In db/db mice, treatment with dapagliflozin(1 mg/kg;6 weeks;i.g.) for 6 weeks had little effects on body weight. The fasting blood glucose level significantly declined after the 6-week treatment of dapagliflozin[5]. Dapagliflozin(30mg/kg/day; p.o.) attenuated SGLT2 expression, which could prevent excessive glucose absorption and increase AMPK phosphorylation in HFD-induced obese mice or OA-stimulated HuS-E/2 cells[6]. Dapagliflozin (1mg/kg; i.v.) given pre-ischemia conferred the maximum level of cardioprotection quantified through the decrease in arrhythmia, attenuated infarct size, decreased cardiac apoptosis and improved cardiac mitochondrial function, biogenesis and dynamics, leading to LV function improvement during cardiac I/R injury[7]. Dapagliflozin (1.5 mg/kg;23days; p.o.) provided glomerular protection in mice with protein-overload proteinuria induced by bovine serum albumin (BSA). Dapagliflozin limited proteinuria, glomerular lesions, and podocyte dysfunction and loss[8].
References:
[1]. Dhillon S. Dapagliflozin: A Review in Type 2 Diabetes. Drugs. 2019 Jul;79(10):1135-1146. doi: 10.1007/s40265-019-01148-3. Erratum in: Drugs. 2019 Dec;79(18):2013. PMID: 31236801; PMCID: PMC6879440.
[2]. Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs. 2012 Dec 3;72(17):2289-312. doi: 10.2165/11209910-000000000-00000. PMID: 23170914.
[3]. Plosker GL. Dapagliflozin: a review of its use in patients with type 2 diabetes. Drugs. 2014 Dec;74(18):2191-209. doi: 10.1007/s40265-014-0324-3. PMID: 25389049.
[4]. Li L, Li Q,et,al.Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway. Front Pharmacol. 2021 May 17;12:589273. doi: 10.3389/fphar.2021.589273. PMID: 34093169; PMCID: PMC8176308.
[5]. Wei R, Cui X, et,al. Dapagliflozin promotes beta cell regeneration by inducing pancreatic endocrine cell phenotype conversion in type 2 diabetic mice. Metabolism. 2020 Oct;111:154324. doi: 10.1016/j.metabol.2020.154324. Epub 2020 Jul 23. PMID: 32712220.
[6]. Chiang H, Lee JC, et,al. Delayed intervention with a novel SGLT2 inhibitor NGI001 suppresses diet-induced metabolic dysfunction and non-alcoholic fatty liver disease in mice. Br J Pharmacol. 2020 Jan;177(2):239-253. doi: 10.1111/bph.14859. Epub 2019 Nov 12. PMID: 31497874; PMCID: PMC6989948.
[7]. Lahnwong S, Palee S, et,al. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovasc Diabetol. 2020 Jun 15;19(1):91. doi: 10.1186/s12933-020-01066-9. PMID: 32539724; PMCID: PMC7296726.
[8]. Cassis P, Locatelli M, et,al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy. JCI Insight. 2018 Aug 9;3(15):e98720. doi: 10.1172/jci.insight.98720. PMID: 30089717; PMCID: PMC6129124.
[9]. Xu J, Kitada M, et,al. Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells. Cells. 2021 Jun 10;10(6):1457. doi: 10.3390/cells10061457. PMID: 34200774; PMCID: PMC8230404.
Dapagliflozin 是一种钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂，是一种新型抗糖尿病药物，由于其抑制 SGLT2 介导的肾葡萄糖重吸收的能力而被批准用于治疗 T2DM。除了提供有效的血糖控制外，达格列净还有助于减轻体重、降低心血管死亡率，并可能减缓糖尿病肾病的进展[1-3]。
达格列净(20 µM;24h ) 促进 ACC1 磷酸化和 ACOX1 蛋白表达，促进自噬并减轻 PA 刺激的 LO2 细胞和 HepG2 细胞中的脂质积累[4]。在糖尿病近端肾小管细胞中，Dapaglide(20 µM;48h)通过增加AMPK活性净改善HG诱导的自噬通量减少和抑制mTOR，同时dapagliflozin抑制NF-κB通路炎症改变[9]。
在 db/db 小鼠中，用达格列净（1 mg/kg；6 周；i.g.）治疗 6 周对体重几乎没有影响。达格列净治疗 6 周后空腹血糖水平显着下降[5]。 Dapagliflozin（30mg/kg/天；口服）减弱了 SGLT2 的表达，这可以防止 HFD 诱导的肥胖小鼠或 OA 刺激的 HuS-E/2 细胞中的葡萄糖过度吸收并增加 AMPK 磷酸化[6]。缺血前给予达格列净（1mg/kg；静脉注射）可通过减少心律失常、缩小梗塞面积、减少心脏细胞凋亡和改善心脏线粒体功能、生物发生和动力学来量化最大水平的心脏保护作用，从而导致心脏 I 期间的 LV 功能改善/R 伤害[7]。 Dapagliflozin（1.5 mg/kg；23 天；口服）在牛血清白蛋白 (BSA) 诱导的蛋白质过载蛋白尿小鼠中提供肾小球保护。达格列净限制蛋白尿、肾小球病变以及足细胞功能障碍和丢失[8]。
| Cell experiment [1]: | |
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Cell lines |
Human hepatocyte-derived liver cells (LO2) and human hepatocellular carcinoma cells (HepG2) |
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Preparation Method |
Cells cultured in DMEM supplemented with 10% FBS at 37 ⊿in a humidified incubator containing 5% CO2, the cells were treated with 0.3 mM PA for 24 h to create the hepatocyte steatosis model in vitro. Then, hepatocytes were exposed to dapagliflozin at a concentration of 20 µM with or without chloroquine for 24 h. |
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Reaction Conditions |
20 µM;24h |
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Applications |
Exposure to 0.3 mM PA for 24 h dramatically increased the intracellular lipid accumulation in LO2 cells and HepG2 cells, whereas cotreatment with dapagliflozin could obviously attenuate the PA-induced lipid accumulation in both of hepatic cell lines. |
| Animal experiment [2]: | |
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Animal models |
Eight-week-old male BKS.Cg-Dock7m+/+Leprdb/Nju (db/db) mice |
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Preparation Method |
Mice were group-housed conventionally and maintained on a 12-h light/dark cycle with free access to food and water. After a one-week adaptation, the diabetic condition was confirmed if the fasting blood glucose was 11.1 mmol/L. The diabetic mice were randomly assigned to two groups with 9 mice per group, and treated by daily intragastric administration of 1 mg/kg dapagliflozin or vehicle (water) for 6 weeks. |
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Dosage form |
1 mg/kg;6 weeks;i.g. |
|
Applications |
In db/db mice, treatment with dapagliflozin for 6 weeks had little effects on body weight. The fasting blood glucose level significantly declined after the 6-week treatment of dapagliflozin. |
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References: [1]. Li L, Li Q, et,al.Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway. Front Pharmacol. 2021 May 17;12:589273. doi: 10.3389/fphar.2021.589273. PMID: 34093169; PMCID: PMC8176308. |
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| Cas No. | 461432-26-8 | SDF | |
| 别名 | 达格列净; BMS-512148 | ||
| 化学名 | (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol | ||
| Canonical SMILES | CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)C3C(C(C(C(O3)CO)O)O)O)Cl | ||
| 分子式 | C21H25ClO6 | 分子量 | 408.87 |
| 溶解度 | ≥ 15.1mg/mL in DMSO, ≥ 116.6 mg/mL in EtOH | 储存条件 | Store at-20°C,sealed storage, away from moisture |
| 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 | 2.4458 mL | 12.2288 mL | 24.4577 mL |
| 5 mM | 0.4892 mL | 2.4458 mL | 4.8915 mL |
| 10 mM | 0.2446 mL | 1.2229 mL | 2.4458 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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Quality Control & SDS
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- Purity: >98.00%
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