KGA-2727

KGA-2727 is a first selective, high-affinity and orally active SGLT1 inhibitor with K_is of 97.4 nM and 43.5 nM for human and rat SGLT1, respectively. The selectivity ratios (K_i for SGLT2/K_i for SGLT1) of KGA-2727 are 140 (human) and 390 (rat). KGA-2727 has antidiabetic efficacy^[1]. IC50 & Target: Ki: 97.4 nM (human SGLT1), 43.5 nM (rat SGLT1)^[1] 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].