Lesogaberan (AZD-3355) napadisylate 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 8.6 nM。通过脑膜中 [3H]GABA 结合位移测量，Lesogaberan napadisylate 对大鼠 GABAB和 GABAA受体的亲和力 (Kis)：分别为 5.1 nM 和 1.4 μM。Lesogaberan napadisylate 通过外周作用模式抑制短暂的食管下括约肌松弛。
| 生物活性 | Lesogaberan (AZD-3355) napadisylate is a potent and selectiveGABABreceptoragonist with anEC50of 8.6 nM for human recombinant GABABreceptors. The affinity (Kis) of Lesogaberan napadisylate for rat GABABand GABAAreceptors, as measured by displacement of [3H]GABA binding in brain membranes: 5.1 nM and 1.4 μM, respectively. Lesogaberan napadisylate inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action[1]. |
| IC50& Target | Ki: 5.1±1.2 nM (rat GABAB), 1.4±0.3 μM (rat GABAA)[1]
EC50: 8.6±0.77 nM (human GABABreceptor)[1] |
体外研究
(In Vitro) | Lesogaberan (3-30 nM) enhances human islet cell proliferation in vitro[2].
Cell Proliferation Assay[2] | 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. |
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体内研究
(In Vivo) | Lesogaberan (AZD3355) potently stimulates recombinant human GABABreceptors 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] | | 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[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
