Dapagliflozin (Synonyms: da格列净; BMS-512148)
Dapagliflozin (BMS-512148) 是一种竞争性葡萄糖协同转运蛋白2 (SGLT2) 抑制剂，可导致尿液中葡萄糖的排泄，用于糖尿病 (DM) 的研究。Dapagliflozin 诱导 HIF1 表达并减轻肾脏 IR 损伤。
生物活性
Dapagliflozin (BMS-512148), a new type of drug used to treat diabetes mellitus (DM), is a competitive sodium/glucose cotransporter 2 (SGLT2) inhibitor, which results in excretion of glucose into the urine[1]. Dapagliflozin induces HIF1 expression and attenuates renal IR injury[2].
IC50 & Target
SGLT2[1]
体外研究(In Vitro)
Dapagliflozin (0-10 μM；24 hours) significantly increases the cell survival in hypoxic HK2 cell in a dose-dependent manner[2].
Dapagliflozin (0-10 μM；2 hours) increases the HIF1 expression, increases AMPK and EKR phosphorylation in hypoxic HK2 cells, but shows no effect on the phosphorylation of AMPK and ERK in normoxic HK2 cells[2]..
Cell Viability Assay[1]
| Cell Line: | Hypoxic HK2 cells |
| Concentration: | 0 μM, 1 μM, 2 μM, 5 μM, 10 μM |
| Incubation Time: | 24 hours |
| Result: | Improved the cell viability in a dose-dependent manner compared with control cells. |
体内研究(In Vivo)
Dapagliflozin (oral administration; 10 mg/kg) causes a marked increase in urinary glucose in SGLT2i-mice, suppresses BAT thermogenesis by reducing sympathetic nerve activity and enhances hepatic gluconeogenesis and glycogenolysis[3].
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03074630 | Amsterdam UMC, location VUmc|Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | May 2016 | Phase 4 | |
| NCT05429593 | Novo Nordisk A+S | June 22, 2022 | Phase 1 | |
| NCT05139914 | Boston University|American Heart Association | May 31, 2022 | Phase 4 |
分子量：408.87
性状：Solid
Formula：C21H25ClO6
CAS 号：461432-26-8
中文名称：达ge列净；达帕格列净；达格列嗪
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
4°C, sealed storage, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性数据
DMSO : ≥ 100 mg/mL (244.58 mM)
H2O : 50 mg/mL (122.29 mM; Need ultrasonic)
* "≥" means soluble, but saturation unknown.
| 浓度溶剂体积质量 | 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 |
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, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-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。
以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶
- 1.
请依序添加每种溶剂： PBS
Solubility: 33.33 mg/mL (81.52 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
- 2.
请依序添加每种溶剂： 5% DMSO 40% PEG300 5% Tween-80 50% saline
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
- 3.
请依序添加每种溶剂： 5% DMSO 95% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
- 4.
请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
- 5.
请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
- 6.
请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
- 7.
请依序添加每种溶剂： 1% DMSO 99% saline
Solubility: ≥ 0.5 mg/mL (1.22 mM); Clear solution
参考文献
[1]. Pedersen MG, et al. Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells. Sci Rep. 2016 Aug 18;6:31214. [Content Brief]
[2]. Chiba Y, et al. Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice. PLoS One. 2016 Mar 10;11(3):e0150756. [Content Brief]
[3]. Chang YK, et al. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury. PLoS One. 2016 Jul 8;11(7):e0158810. [Content Brief]
注：产品仅用于科研
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