Dapagliflozin (BMS-512148) is a novel selective inhibitor of sodium-glucose co-transporter type 2. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of glucuretic, antihyperglycemic drugs that target the process of renal glucose reabsorption and induce glucuresis independently of insulin secretion or action. Dapagliflozin (BMS-512148) inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine. In initial clinical trials, Dapagliflozin 10 mg reduced HbA1c by -0.54% (weighted mean differences (WMD), 95% CI -0.67 to -0.40) compared to placebo. Phase II and III clinical trials have demonstrated that dapagliflozin is a safe and effective method for treating type 2 diabetes. Dapagliflozin (BMS-512148) produces a sustained, dose-dependent reduction in plasma glucose levels while simultaneously improving insulin secretion and sensitivity. Therapy with dapagliflozin also results in a mild osmotic-diuretic effect that may account for decreases in total body weight (~2-3 kg) and blood pressure (systolic 2-5 mm Hg, diastolic 1.5-3 mm Hg), and increases in hematocrit (1-2%).
Cell Experiment | |
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Cell lines | CHO cells |
Preparation method | SGLT Binding Assays. Chinese hamster ovary (CHO) cells stably expressing human SGLT2 (hSGLT2) and human SGLT1 (hSGLT1) (Genbank accession numbers M95549 and M24847, respectively) were utilized for the development of transport assays using the selective SGLT substrate -methyl-D-glucopyranoside (AMG). Inhibitors were assayed for the ability to inhibit [14C]AMG uptake in a protein-free buffer over a 2 h incubation period. The response curve was fitted to an empirical four-parameter model to determine the inhibitor concentration at half maximal response, reported as EC50. Protein-free buffer was used to simulate the low-protein conditions of the glomerular filtrate, which bathes the SGLT targets on the lumenal surface of the proximal tubule in the kidney. |
Concentrations | |
Incubation time | 2 h |
Animal Experiment | |
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Animal models | Normal Sprague Dawley rats |
Formulation | 5% mpyrol, 20% PEG 400, and 20 mM sodium diphosphate |
Dosages | single dose of 0.01-10 mg/kg |
Administration | orally |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Molecular Weight | 408.87 |
Formula | C21H25ClO6 |
CAS Number | 461432-26-8 |
Purity | 99.16% |
Solubility | DMSO 80 mg/mL Ethanol 17 mg/mL |
Storage | at -20°C |
Related SGLT Products |
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Tofogliflozin (hydrate)
Tofogliflozin (CSG-452) hydrate is a potent and highly specific sodium-glucose co-transporter 2(SGLT2) inhibitor with IC50 value of 2.9 nM. |
Luseogliflozin
Luseogliflozin is a SGLT2 inhibitor, it reduced reabsorption of renal filtered glucose and decreased renal glucose threshold (RTG) in urine to increase urinary glucose excretion. |
LX2761
LX2761 is a locally acting SGLT1 and SGLT2 inhibitor in vitro with IC50 values of 2.2 nM and 2.7 nM for hSGLT1 and hSGLT2, respectively. |
Canagliflozin hemihydrate
Canagliflozin hemihydrate (JNJ-28431754; TA 7284) is a highly potent and selective SGLT2 inhibitor for hSGLT2 with IC50 of 2.2 nM. |
Ertugliflozin (PF-04971729)
Ertugliflozin (MK-8835, PF-04971729) is a potent and selective inhibitor of the sodium-dependent glucose cotransporter 2 (SGLT2). |
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