Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes

J Med Chem. 2008 Mar 13;51(5):1145-9. doi: 10.1021/jm701272q. Epub 2008 Feb 9.

Abstract

The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzhydryl Compounds
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Glucosides / chemical synthesis*
  • Glucosides / chemistry
  • Glucosides / pharmacology
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Kidney / metabolism*
  • Rats
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Stereoisomerism

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors