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Dapagliflozin(BMS-512148)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Dapagliflozin(BMS-512148)图片
CAS NO:461432-26-8
规格:≥98%
包装与价格:
包装价格(元)
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)408.87
FormulaC21H25ClO6
CAS No.461432-26-8
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 82 mg/mL (200.6 mM)
Water: <1 mg/mL
Ethanol: 17 mg/mL (41.5 mM)
Solubility (In vivo)30% PEG400+0.5% Tween80+5% Propylene glycol: 30 mg/mL
SynonymsBMS-512148; trade name Farxiga in the US and Forxiga in the EU; BMS512148; BMS 512148;
实验参考方法
In Vitro

In vitro activity: Dapagliflozin is not sensitive to hSGLT1 with a 1200-fold IC50. Dapagliflozin is 32-fold more potent than phlorizin against hSGLT2 but 4-fold less than phlorizin against hSGLT1. Dapagliflozin is highly selective versus GLUT transporters and displays 8–9% inhibition in protein-free buffer at 20 μM and virtually no inhibition in the presence of 4% bovine serum albumin. Dapagliflozin has good permeability across Caco-2 cell membranes and is a substrate for P-glycoprotein (P-gp) but not a significant P-gp inhibitor. Dapagliflozin is stable in rat, dog, monkey, and human serum at 10 μM. Dapagliflozin shows no inhibitory responses or induction to human P450 enzymes. The in vitro metabolic pathways Dapagliflozin are glucuronidation, hydroxylation, and O-deethylation


Kinase Assay: EC50 values of 1.1 nM for hSGLT2 and 1.4 μM for hSGLT1 determined for Dapagliflozin corresponded to 1200-fold selectivity for SGLT2 as compared with phlorizin’s 10-fold selectivity. Dapagliflozin inhibitory potencies against rat SGLT (rSGLT)2 and hSGLT2 were comparable, but the selectivity of Dapagliflozin for rSGLT2 versus rSGLT1 decreased to 200-fold


Cell Assay: To perform the cell survival assay, cells are collected after 24 h incubation with vehicle or dapagliflozin pretreatment in 30-min ischemia and surviving cells are counted with Trypan blue staining. The percentage survival is determined by quantization of the relative viable number of treated cells divided by the viable number of untreated cells.

In VivoDapagliflozin reduces blood glucose levels by 55% after 0.1 mg/kg oral dose in hyperglycemic streptozotocin (STZ) rats, which is in part to the metabolic stability conferred by the C-glucoside linkage. Dapagliflozin displays a favorable absorption, distribution, metabolism, and excretion (ADME) profile and is orally bioavailable. Dapagliflozin (1 mg/kg) causes significant dose-dependent glucosuria and increase in urine volume in normal rats over 24 hours post-dose. Dapagliflozin induces increase in urine glucose and urine volume excretion at 6 hours post-dose in Zucker diabetic fatty (ZDF) rats. Dapagliflozin lowers fasting and fed glucose levels in ZDF rats even by 2 weeks of treatment, without any marker of renal or liver toxicity. Dapagliflozin significantly reduces the development of hyperglycaemia, with lowered blood glucose. Dapagliflozin could improve the insulin sensitivity, reduce β-cell mass and the development of impaired pancreatic function.
Animal modelNormal Sprague Dawley rats or streptozotocin induced male Sprague Dawley rats
Formulation & DosageDissolved in 5% mpyrol, 20% PEG400, and 20 mM sodium diphosphate; 0.01-10 mg/kg (1 mL/kg) followed by a 50% glucose solution (2 g/kg); oral administration.
ReferencesJ Med Chem. 2008 Mar 13;51(5):1145-9; Diabetes. 2008 Jun;57(6):1723-9.