Lesogaberan

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

Lesogaberan (AZD-3355) 是一种有效、选择性、外周作用的 GABAB 受体激动剂，Ki 为 5 nM，EC50 为 8.6 nM，选择性是 GABAA (Ki=1.4 uM) 的 274 倍。

Lesogaberan (AZD-3355) is a potent, selective, peripherally acting GABAB receptor agonist with Ki of 5 nM and EC50 of 8.6 nM, 274-fold selectivity over GABAA (Ki=1.4 uM); potently stimulates recombinant human GABAB receptors and inhibits transient lower esophageal sphincter relaxation (TLESR) through a peripheral mode of action in vivo, shows potential for treatment of GERD.Other Indication Phase 2 Discontinued.

Lesogaberan (3-30 nM) enhances human islet cell proliferation in vitro.Cell Proliferation Assay Cell Line:Human islet cells Concentration:3, 10, and 30 nM Incubation Time:4 days Result:Had a small but nonsignificant promitotic effect at 3?nM, while treatment at higher dosages (10 and 30?nM) led to a 2-3-fold increase in proliferation relative to that of islets cultured in medium alone.

Lesogaberan (AZD3355) potently stimulates recombinant human GABAB receptors and inhibits transient lower esophageal sphincter relaxation (TLESR) in dogs, with a biphasic dose-response curve.Oral Lesogaberan (0.08?mg/mL; 48 hours) protects human islet β-cells from apoptosis in islet grafts in mice. Lesogaberan (7 μmol/kg) shows high oral availability (88% in the dog and 100% in the rat) and relatively low systemic clearance in female Sprague Dawley rats. Animal Model:Diabetic NOD/scid mice were implanted with human islets Dosage:0.08 mg/mL Administration:Oral feeding; 48 hours Result:Significantly reduced the percentages of apoptotic islet cells and increased the frequency of insulin+ β-cells in human islet grafts. Animal Model:Female Sprague Dawley rats Dosage:7 μmol/kg (Pharmacokinetic Analysis)Administration:Oral Result:High oral availability (88% in the dog and 100% in the rat) and relatively low systemic clearance. Plasma protein binding was 1% in rat and human plasma.

AZD-3355

Membrane Transporter/Ion Channel

GAT

GAT

Other Indications

Other Disease

344413-67-8

141.082

C3H9FNO2P

>98% (HPLC)

——

O=P(C[C@H](F)CN)O

((R)-3-Amino-2-fluoropropyl)phosphinic acid

(-20℃)

With Ice Pack

≥ 2 years