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Dapagliflozin

Cat. No. M1937
Dapagliflozin Structure
Synonym:

BMS-512148

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mM*1mL in DMSO USD 50  USD50 In stock
5mg USD 50  USD50 In stock
10mg USD 70  USD70 In stock
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Quality Control
Biological Activity

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%).

Protocol
Cell Experiment
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
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
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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.

Chemical Information
Molecular Weight 408.87
Formula C21H25ClO6
CAS Number 461432-26-8
Purity 99.16%
Solubility DMSO 80 mg/mL
Storage -20°C, dry, sealed
References

[1] Clar C, et al. BMJ Open. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes.

[2] Whaley JM, et al. Diabetes Metab Syndr Obes. Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus.

[3] Shah NK, et al. Pharmacotherapy. Dapagliflozin: a novel sodium-glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus.

[4] Meng W, et al. J Med Chem. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.

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Ertugliflozin L-pyroglutamic acid

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Tofogliflozin (hydrate)

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Keywords: Dapagliflozin, BMS-512148 supplier, SGLT, inhibitors

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