Dapagliflozin (Synonyms: da格列凈; BMS-512148)
Dapagliflozin (BMS-512148) 是一種競(jìng)爭(zhēng)性葡萄糖協(xié)同轉(zhuǎn)運(yùn)蛋白2 (SGLT2) 抑制劑，可導(dǎo)致尿液中葡萄糖的排泄，用于糖尿病 (DM) 的研究。Dapagliflozin 誘導(dǎo) HIF1 表達(dá)并減輕腎臟 IR 損傷。
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]
體外研究(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. |
體內(nèi)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
性狀：Solid
Formula：C21H25ClO6
CAS 號(hào)：461432-26-8
中文名稱：達(dá)ge列凈；達(dá)帕格列凈；達(dá)格列嗪
運(yùn)輸條件
Room temperature in continental US; may vary elsewhere.
儲(chǔ)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)
溶解性數(shù)據(jù)
DMSO : ≥ 100 mg/mL (244.58 mM)
H2O : 50 mg/mL (122.29 mM; Need ultrasonic)
* "≥" means soluble, but saturation unknown.
| 濃度溶劑體積質(zhì)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 |
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；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)月內(nèi)使用，-20°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)月內(nèi)使用。
以下溶解方案都請(qǐng)先按照 In Vitro 方式配制澄清的儲(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，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的方式助溶
- 1.
請(qǐng)依序添加每種溶劑： PBS
Solubility: 33.33 mg/mL (81.52 mM); Clear solution; Need ultrasonic and warming and heat to 60°C
- 2.
請(qǐng)依序添加每種溶劑： 5% DMSO 40% PEG300 5% Tween-80 50% saline
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
- 3.
請(qǐng)依序添加每種溶劑： 5% DMSO 95% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
- 4.
請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
- 5.
請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
- 6.
請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
- 7.
請(qǐng)依序添加每種溶劑： 1% DMSO 99% saline
Solubility: ≥ 0.5 mg/mL (1.22 mM); Clear solution
參考文獻(xiàn)
[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：產(chǎn)品僅用于科研
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