Cell lines

HK2 cells

Preparation method

The solubility of this compound in DMSO is > 20.75 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

100 or 500 nM; 72 hrs

Applications

In HK2 cells, Empagliflozin blocked SGLT2 without causing a compensatory increase in the other glucose transporters. Empagliflozin at both concentrations significantly inhibited high glucose-induced TLR4 expression by 97.2 ± 8.2% and 64.4 ± 12.6%, respectively. Besides, at the dose of 500 nM, Empagliflozin significantly inhibited high glucose-induced NF- κB binding by 91.7 ± 14.9%. In addition, Empagliflozin reduced high glucose-induced secretion of IL-6 by 92.0 ± 11.7% and 116.5 ± 19.6% at the doses of 100 and 500 nM, respectively.

Animal models

ZDF rats and beagle dogs

Dosage form

2 mL/kg; i.v. or p.o.

Applications

Empagliflozin achieved high exposure in dogs, with plasma concentrations > 100-fold above the IC50 value (measured 24 hrs after administration). In ZDF rat, the total plasma clearance of Empagliflozin was 43 mL/min/kg, while in dogs, was lower at 1.8 mL/min/kg. The Cmax values of Empagliflozin for ZDF rat and dogs were 167 nM and 17254 nM, respectively.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.