Empagliflozin is a Sodium-Glucose Cotransporter 2 Inhibitor. The mechanism of action of empagliflozin is as a Sodium-Glucose Transporter 2 Inhibitor.

Empagliflozin长期治疗可改善糖尿病大鼠血糖控制和代谢综合征的特征.5 mg/kg Empagliflozin处理狗24小时,血浆浓度比测量的IC50值高100倍以上.Empagliflozin在ZDF大鼠中的总血浆清除率为43mL/min/kg,而狗中的血浆清除率为1.8mL/min/kg. Empagliflozin处理ZDF大鼠和狗的Cmax分别为167 nM和17254 nM.empagliflozin在ZDF大鼠中的生物利用度为33.2％,而狗中的高达89.0％.

动力学结合实验中,[3H]-Empagliflozin在不存在葡萄糖的情况下对SGLT-2表现出高的亲和力,平均Kd为57 nM,[3H]-Empagliflozin结合到SGLT-2的半衰期为59分钟。Empagliflozin与葡萄糖竞争性结合到SGLT-2。Empagliflozin对hSGLT-2比hSGLT-1（IC50 8300 nM）选择性高2500倍,比hSGLT-4选择性高3500倍以上,比hSGLT-5选择性高350倍以上（IC50 = 1100 nM）,比hSGLT-6选择性高600倍以上。10 μM Empagliflozin对GLUT1没有抑制作用。

[14C]-monosaccharide uptake inhibition experiments: Stable cell lines over-expressing hSGLT-1, -2, -4, -5 or -6 or rSGLT-1 or -2 are used for the sodium-dependent monosaccharide transport inhibition assay. Cells are pre-incubated in 200 μL uptake buffer (10 mM HEPES, 137 mM NaCl, 5.4 mM KCl, 2.8 mM CaCl2, 1.2 mM MgCl2, 50 μg/ml Gentamycin, 0.1% BSA) for 25 minutes at 37°C. 10 μM Cytochalasin B and test compound is added at different concentrations 15 minutes before the initiation of the uptake experiment. The uptake reaction is started by the addition of 0.6 μCi [14C]-labelled monosaccharide i.e. [14C]-labelled AMG, glucose, fructose, mannose or myo-inositol, in 0.1 mM AMG (or the respective non-radioactive monosaccharide). After incubation for 60 minutes (hSGLT-5), 90 minutes (hSGLT-4) or 4 hours (hSGLT-2) at 37°C, the cells are washed three times with 300 μL PBS and then lysed in 0.1 N NaOH with intermittent shaking for 5 minutes. The lysate is mixed with 200 μL MicroScint 40 and shaken for 15 minutes and counted for radioactivity in the TopCount NXT. For SGLT-4 and SGLT-5 assays cells are pre-incubated in pre-treatment buffer (uptake buffer containing choline chloride instead of NaCl) for 25 minutes prior to addition of uptake buffer.

MTS assay(Only for Reference)

864070-44-0

C23H27ClO7

450.91

BI 10773;恩格列净;Empagliflozin

[1]Grempler R, et al. Diabetes Obes Metab, 2012, 14(1), 83-90. [2]Kim P, Kim G Y, Cho M Y, et al. Manufacture and Characterization of Two Distinct Quasi-polymorphs of Empagliflozin[J]. Journal of Crystal Growth. 2020: 125489. [3]Thomas L, et al. Diabetes Obes Metab, 2012, 14(1), 94-96. [4]Sakaeda T, et al. Susceptibility to serious skin and subcutaneous tissue disorders and skin tissue distribution of sodium-dependent glucose co-transporter type 2 (SGLT2) inhibitors. Int J Med Sci. 2018 Jun 13;15(9):937-943. [5]Panchapakesan U, et al. PLoS One, 2013, 8(2), e54442.

[1]Tian G, Yu Y, Deng H, et al. Empagliflozin alleviates ethanol‐induced cardiomyocyte injury through inhibition of mitochondrial apoptosis via a SIRT1/PTEN/Akt pathway. Clinical and Experimental Pharmacology and Physiology. 2021, 48(6): 837-845. [2]Kim P, Kim G Y, Cho M Y, et al. Manufacture and Characterization of Two Distinct Quasi-polymorphs of Empagliflozin. Journal of Crystal Growth. 2020: 125489

DMSO:83 mg/mL (184.1 mM)
Ethanol:<1 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years