Biological Activity
KGA-2727 is a potent, selective SGLT1 inhibitor with Ki of 97.4 nM, >100-fold selectivity over SGLT2; attenuates the elevation of plasma glucose after glucose loading in streptozotocin-induced diabetic rats, preserves glucose-stimulated insulin secretion and reduces urinary glucose excretion with improved morphological changes of pancreatic islets and renal distal tubules in ZDF rats.
In Vitro
A Dixon plot analysis for KGA-2727 displays good linearity for human SGLT1 and SGLT2. The results of the Dixon plot show that KGA-2727 inhibits these SGLTs in a competitive manner. KGA2727 dose-dependently inhibits Methyl-Dglucopyranoside (AMG) uptake by SGLT1 and SGLT2[1].
In Vivo
In the oral glucose tolerance test with streptozotocin-induced diabetic rats, KGA-2727 attenuates the elevation of plasma glucose after glucose loading, indicating that KGA-2727 improves postprandial hyperglycemia[1]. In Zucker diabetic fatty (ZDF) rats, chronic treatments with KGA-2727 reduces the levels of plasma glucose and glycated hemoglobin. Furthermore, KGA-2727 preserves glucose-stimulated insulin secretion and reduces urinary glucose excretion with improved morphological changes of pancreatic islets and renal distal tubules in ZDF rats[1].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.