product name Dapagliflozin
Description: Dapagliflozin, also known as BMS-512148, is a potent and selective hSGLT2 inhibitor with EC50 of 1.1 nM, it exhibits1200-fold selectivity over hSGLT1. Dapagliflozin was approved in 2012 by FDAfor the treatment of type 2 diabetes. Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes blood glucose to be eliminated through the urine.
References: J Med Chem. 2008 Mar 13;51(5):1145-9; Diabetes. 2008 Jun;57(6):1723-9.
408.87
Formula
C21H25ClO6
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
Synonyms
BMS-512148
other peoduct :
| 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: |
|---|---|
| In Vivo | Dapagliflozin 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 model | Normal Sprague Dawley rats or streptozotocin induced male Sprague Dawley rats |
| Formulation & Dosage | Dissolved 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. |
| References | J Med Chem. 2008 Mar 13;51(5):1145-9; Diabetes. 2008 Jun;57(6):1723-9. |
