KGA-2727

KGA-2727 is a potent and selective SGLT1 inhibitor, with Kis of 97.4 nM and 43.5 nM for human and rat SGLT1, respectively. The selectivity ratios (Ki for SGLT2/Ki for SGLT1) of KGA-2727 are 140 (human) and 390 (rat) . KGA-2727 for the treatment of diabete.KGA-2727, which has a pyrazole-O-glucoside structure, as the first selective SGLT1 inhibitor. KGA-2727 inhibited SGLT1 potently and highly selectively in an in vitro assay using cells transiently expressing recombinant SGLTs.KGA2727 dose-dependently inhibits Methyl-Dglucopyranoside (AMG) uptake by SGLT1 and SGLT2. A Dixon plot analysis for KGA-2727 shows good linearity for human SGLT1 and SGLT2. KGA-2727 inhibits these SGLTs in a competitive manner displayed from the results of the Dixon plot.In a small intestine closed loop absorption test with normal rats, KGA-2727 inhibited the absorption of glucose but not that of fructose. After oral intake of starch along with KGA-2727 in normal rats, the residual content of glucose in the gastrointestinal tract increased. In the oral glucose tolerance test with streptozotocin-induced diabetic rats, KGA-2727 attenuated the elevation of plasma glucose after glucose loading, indicating that KGA-2727 improved postprandial hyperglycemia. In Zucker diabetic fatty (ZDF) rats, chronic treatments with KGA-2727 reduced the levels of plasma glucose and glycated hemoglobin. Furthermore, KGA-2727 preserved glucose-stimulated insulin secretion and reduced urinary glucose excretion with improved morphological changes of pancreatic islets and renal distal tubules in ZDF rats. In addition, the chronic treatment with KGA-2727 increased the level of glucagon-like peptide-1 in the portal vein.

666842-36-0

>98% (HPLC)

DMSO:100 mg/mL (186.35 mM; Need ultrasonic)

O=C (N) CCNCCCOC1=CC=C (CC2=C (C (C) C) NN=C2O[C@H]3[C@@H] ([C@H] ([C@@H] ([C@@H] (CO) O3) O) O) O) C (C) =C1

C26H40N4O8

536.62

Storage temperature: -20°C. Stability: ≥ 2 years