Lesogaberan(AZD-3355)是一种有效的选择性GABAB受体激动剂，对人重组GABAB受体的EC50为8.6nM。对大鼠脑GABAB和GABAA受体的结合亲和力(Ki)分别为5.1nM和1.4μM。
Lesogaberan (AZD-3355) is a potent and selective GABAB receptor agonist with an EC50 of 8.6 nM for human recombinant GABAB receptors. Binding affinity (Kis) of 5.1 nM and 1.4 μM for rat brain GABAB and GABAA receptors, respectively[1].
Lesogaberan (3-30 nM) enhances human islet cell proliferation in vitro[2]. Cell Proliferation Assay[2] Cell Line: Human islet cells
Lesogaberan (AZD3355) potently stimulates recombinant human GABAB receptors and inhibits transient lower esophageal sphincter relaxation (TLESR) in dogs, with a biphasic dose-response curve[1].Oral Lesogaberan (0.08 mg/mL; 48 hours) protects human islet β-cells from apoptosis in islet grafts in mice[2]. Lesogaberan (7 μmol/kg) shows high oral availability (88% in the dog and 100% in the rat) and relatively low systemic clearance in female SpragueDawley rats[1]. Animal Model: Diabetic NOD/scid mice were implanted with human islets[2]
[1]. Lehmann A, et al. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther. 2009 Nov;331(2):504-12. [2]. Tian J, et al. Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication. J Diabetes Res. 2017;2017:6403539.
动态评分
0.0