生物活性

• 靶点	SGLT2 IC50:3.1nM

• 描述Sodium glucose cotransporter-2 (SGLT-2) is responsible for glucose reabsorption via the kidney. Empagliflozin is a selective SGLT-2 inhibitor that blocks the uptake of [¹⁴C]-AMG via human SGLT-2 (hSGLT-2) with an IC50 value of 3.1nM in vitro. It exhibited >2500-, >3500-, >350-, and >600-fold selectivity over hSGLT-1 (IC50 = 8.3μM), hSGLT-4 (IC50 = 11μM), hSGLT-5 (IC50 = 1.1μM), and hSGLT-6 (IC50 = 2.0μM), respectively. In kinetic binding experiments, [³H]-empagliflozin showed a high affinity for SGLT-2 (K_d = 57nM) in the absence of glucose, whereas glucose at 20nM lowered the affinity of empagliflozin to a K_d value of 194nM^[8]. In db/db mice, treatment with empagliflozin (10mg/kg/day in food) for 4 weeks decreased the ventricular mass, lowered the fasting glucose level and elevated the fed and fasted ketone levels as compared to the vehicle-treated group. In the presence of insulin, empagliflozin-treated db/db mice showed increased mean palmitate oxidation rate in the heart in comparison to C57BL/6J mice. The cardiac ATP production rate in vehicle-treated db/db mice was 36% lower than that in C57BL/6J mice, whereas empagliflozin treatment restored the ATP production rate to the level similar to that in C57BL/6J mice^[9].
• 作用机制Empagliflozin is a potent and selective inhibitor of SGLT-2. It binds to SGLT-2 in a glucose-competitive manner^[8].

• 动物研究
  剂量	Rat: 3 mg/kg, 10 mg/kg[3] (p.o.), 10 mg/kg - 30 mg/kg[4] (i.g.) Mice: 3 mg/kg, 10 mg/kg[5] (p.o.), 35 mg/kg[6] (p.o.)
  给药途径	p.o., i.g.
  动物药代数据	Animal Mice[7] Dose 5 mg/kg (i.v., male) 250 mg/kg (p.o., male) Administration i.v. p.o. MRT 0.488 h (i.v.) 2.52 h (p.o.) F 89.8% (p.o.) T1/2 1.26 h (i.v.) 5.59 h (p.o.) Tmax 0.67 h (p.o.) CL 40.1 ml/min/kg (i.v.) 44.6 ml/min/kg (p.o.) Cmax 97700 nM (p.o.) Vss 1.17 L/kg (i.v.) AUC 4610 μM·h (i.v.) 207000 μM·h (p.o.)