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Empagliflozin (BI 10773)

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Catalog No.
A4601
SGLT2抑制剂,用于口服治疗2型糖尿病
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
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5mg
¥ 500.00
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10mg
¥ 700.00
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50mg
¥ 1,700.00
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100mg
¥ 2,700.00
现货

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Background

Empagliflozin is a selective inhibitor of SGLT-2 with IC50 value of 3.1 nM [1].

Sodium glucose cotransporter-2 (SGLT-2) is a member of sodium glucose co-transporter family and plays a pivotal role in glucose reabsorption in the kidney [2].

Empagliflozin is a potent SGLT-2 inhibitor and has a high degree of selectivity over SGLT-1, 4, 5 and 6 than other reported SGLT-2 inhibitors. When tested with a panel of human cell lines over-expressed SGLT-1, 2, 4, 5 and 6, Empagliflozin treatment competitively bind to SGLT-2 over glucose at low dose [1]. In human proximal tublular cell (PTC) cell line HK2 cells, Empagliflozin treatment for 72 h inhibits the expression of SGLT-2 which in turn reversed high glucose induced TLR4 expression, NF-κB binding, IL-6 secretion, AP-1 binding and CIV expression [3].

In Zucker diabetic fatty rat model, oral administration of Empagliflozin shows good efficiency with moderate total plasma clearance (CL) and bioavailability (BA) which indicated that Empagliflozin as an innovative therapeutic approach to treat diabetes in clinic [1]. When treated Zucker diabetic fatty rat model with Empagliflozin, both single and multiple doses results in the urinary glucose excretion and reductions in blood glucose levels [4].

References:
[1].  Grempler, R., et al., Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab, 2012. 14(1): p. 83-90.
[2].  Ndefo, U.A., et al., Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. P t, 2015. 40(6): p. 364-8.
[3].  Panchapakesan, U., et al., Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy? PLoS One, 2013. 8(2): p. e54442.
[4].   Thomas, L., et al., Long-term treatment with empagliflozin, a novel, potent and selective SGLT-2 inhibitor, improves glycaemic control and features of metabolic syndrome in diabetic rats. Diabetes Obes Metab, 2012. 14(1): p. 94-6.

文献引用

1. Zhou Y, Fan J, et al. "SGLT-2 inhibitors reduce glucose absorption from peritoneal dialysis solution by suppressing the activity of SGLT-2." Biomed Pharmacother. 2019 Jan;109:1327-1338. PMID:30551383
2. Bahia Abbas Moussa, Marianne Alphonse Mahrouse, et al. "Different resolution techniques for management of overlapped spectra: Application for the determination of novel co-formulated hypoglycemic drugs in their combined pharmaceutical dosage form." Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy Available online 20 June 2018.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt450.91
Cas No.864070-44-0
FormulaC23H27ClO7
Solubility≥20.75mg/mL in DMSO, ≥7.06 mg/mL in EtOH with ultrasonic, <2.59 mg/mL in H2O
Chemical Name(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
SDFDownload SDF
Canonical SMILESC1COCC1OC2=CC=C(C=C2)CC3=C(C=CC(=C3)C4C(C(C(C(O4)CO)O)O)O)Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

HK2细胞

制备方法

在DMSO中的溶解度大于20.75 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

100或500 nM;72小时

实验结果

在HK2细胞中,Empagliflozin阻断SGLT2,而不会引起其它葡萄糖转运蛋白的代偿性增加。 在2种浓度下,Empagliflozin显著抑制高浓度葡萄糖诱导的TLR4表达(分别为97.2 ± 8.2%和64.4 ± 12.6%)。在500 nM的剂量下,Empagliflozin显著抑制高浓度葡萄糖诱导的NF-κB结合(91.7 ± 14.9%)。此外,Empagliflozin在100 nM和500 nM的剂量下使高浓度葡萄糖诱导的IL-6分泌分别降低了92.0 ± 11.7%和116.5 ± 19.6%。

动物实验 [2]:

动物模型

ZDF大鼠和比格犬

给药剂量

2 mL/kg;静脉注射或口服给药

实验结果

Empagliflozin在比格犬中显示出较高的暴露量,其血浆浓度高于IC50值100倍以上(给药后24小时进行测定)。在ZDF大鼠中,Empagliflozin的总血浆清除率为43 mL/min/kg,而在比格犬中,总血浆清除率较低,为1.8 mL/min/kg。Empagliflozin对ZDF大鼠和比格犬的Cmax值分别为167 nM和17254 nM。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Panchapakesan, U., et al., Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy PLoS One, 2013. 8(2): p. e54442.

[2]. Grempler, R., et al., Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab, 2012. 14(1): p. 83-90.

生物活性

Description Empagliflozin (BI 10773) is a selective, potent and dose-depentent inhibitor of SGLT-2(sodium glucose cotransporter-2) with IC50 values of 3.1 nM, 8300 nM, 11000 nM, 1100 nM and 2000 nM, for SGLT-2,1,4,5 and 6, respectively.
Targets SGLT-2          
IC50 3.1 nM          

质量控制

化学结构

Empagliflozin (BI 10773)

相关生物数据

Empagliflozin (BI 10773)

相关生物数据

Empagliflozin (BI 10773)

相关生物数据

Empagliflozin (BI 10773)