KGA-2727

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.

Research Areas >> Metabolic Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> SGLT

Ki: 97.4 nM (human SGLT1), 43.5 nM (rat SGLT1)[1]

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 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].

[1]. Shibazaki T, et al. KGA-2727, a novel selective inhibitor of a high-affinity sodium glucose cotransporter (SGLT1), exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther. 2012 Aug;342(2):288-96.