生物活性

• 靶点	SGLT2 EC50:1.1nM

• 描述The sodium-dependent glucose transport (SGLT) proteins belong to the sodium glucose cotransporter family. Sodium-dependent glucose transport 2 (SGLT2) is a high-capacity, low-affinity transporter that is expressed mainly in the kidney. It has a Na(+) to glucose coupling ratio of 1:1. It is estimated that 90% of renal glucose reabsorption is facilitated by SGLT2 residing on the surface of the epithelial cells lining the S1 segment of the proximal tubule. Dapagliflozin is a potent and selective SGLT2 inhibitor. In an experiment system of Chinese hamster ovary cells stably expressing human SGLT2 and SGLT1, data yielded by monitoring inhibition of AMG showed that the EC50 of dapagliflozin for human SGLT2 inhibition was 1.1 nM, while that for human SGLT1 was 1390 nM^[7]. In acute normal and diabetic rat studies, SD or ZDF rats were dosed orally with single doses of dapagliflozin at 0.01 mg/kg, 0.1 mg.kg, 1 mg/kg or 10 mg/kg. In normal rats， the results were that dapagliflozin caused significant dose-dependent glucosuria and increase in urine volume, with 1 mg/kg producing a 400-fold increase in urine glucose and a threefold increase in urine volume versus vehicle over 24 h post-dose. Dapagliflozin administration was also associated with a reduction in glucose area under the curve over 1 h post-dose at 1 and 10 mg/kg doses in the glucose tolerance test in normal rats. In ZDF rats, dapagliflozin dose-dependently increased urine glucose and urine volume excretion at 6 h post-dose ^[8]. In another study, dapagliflozin was administrated at the dose of 0.5 mg/kg orally once daily for 15 days. When measured 24 h after the final dose on day 15, ZDF rats treated with dapagliflozin displayed a 53% decrease in 18-h FPG level compared with vehicle-treated rats^[8].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  CHO cells	-	Function assay	2 h	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50=0.00049 μM	20434909
  CHOK1 cells	-	Function assay	3 h	Inhibition of human SGLT2 expressed in CHOK1 cells assessed as inhibition of [14C]-AMG uptake after 3 hrs by microbeta scintillation counting analysis, IC50=0.001 μM	24842618
  COS-7 cells	-	Function assay	2 h	Inhibition of human SGLT1 transfected in COS-7 cells assessed as AMG uptake after 2 hrs by scintillation counting, IC50=0.89 μM	19896374

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• 动物研究
  剂量	Rat: 0.1 mg/kg - 1 mg/kg[3] (p.o.); 10 mg/kg[4] (i.p.), 75 mg/kg, 150 mg/kg[5] (i.p.)
  给药途径	p.o., i.p.
  动物药代数据	Animal Rats[6] Dose 1 mg/kg Administration p.o. F 0.84 T1/2 4.6 h Tmax 1.7 h CL 4.8 ml/min/kg Cmax 0.6 µg/mL Vss 1.6 L/kg

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02096705	Diabetes	Phase 3	Completed	-	-
  NCT03565458	Type 2 Diabetes Mellitus	Phase 1	Active, not recruiting	December 22, 2018	Korea, Republic of ... more >> LG chem Seoul, Gangseo-Gu, Korea, Republic of, 07795 Collapse <<
  NCT02096705	-	-	Completed	-	-

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