| Bioactivity | KGA-2727 is a first selective, high-affinity and orally active 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 has antidiabetic efficacy[1]. |
| Target | Ki: 97.4 nM (human SGLT1), 43.5 nM (rat SGLT1) |
| Invitro | 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]. |
| Name | KGA-2727 |
| CAS | 666842-36-0 |
| Formula | C26H40N4O8 |
| Molar Mass | 536.62 |
| Appearance | Solid |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | 4°C, protect from light *In solvent : -80°C, 6 months; -20°C, 1 month (protect from light) |
| Reference | [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. |