KGA-2727

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

KGA-2727 是一种有效的选择性 SGLT1 抑制剂，对人和大鼠 SGLT1 的 Ki 值分别为 97.4 nM 和 43.5 nM。 KGA-2727 的选择性比（SGLT2 的 Ki/SGLT1 的 Ki）为 140（人）和 390（大鼠）。 KGA-2727用于治疗糖尿病。KGA-2727具有吡唑-O-葡萄糖苷结构，作为第一个选择性SGLT1抑制剂。

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.

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.

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. 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.

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GPCR/G Protein

SGLT

SGLT1

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666842-36-0

536.62

C26H40N4O8

>98% (HPLC)

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

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(-20℃)

With Ice Pack

≥ 2 years