Lesogaberan (AZD-3355) hydrochloride 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 hydrochloride 对大鼠 GABAB和 GABAA受体的亲和力 (Kis)：分别为 5.1 nM 和 1.4 μM。Lesogaberan hydrochloride 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) hydrochloride is a potent and selectiveGABABreceptoragonist with anEC50of 8.6 nM for human recombinant GABABreceptor. The affinity (Kis) of Lesogaberan hydrochloride for rat GABABand GABAAreceptors, as measured by displacement of [3H]GABA binding in brain membranes: 5.1 nM and 1.4 μM, respectively. Lesogaberan hydrochloride 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 hydrochloride (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 hydrochloride 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) hydrochloride protects human islet β-cells from apoptosis in islet grafts in mice[2].
Lesogaberan (7 μmol/kg) hydrochloride 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: | 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 | 4°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 240 mg/mL(1351.81 mM;Need ultrasonic) H2O : 100 mg/mL(563.25 mM;Need ultrasonic) 配制储备液 | 1 mM | 5.6325 mL | 28.1627 mL | 56.3253 mL | | 5 mM | 1.1265 mL | 5.6325 mL | 11.2651 mL | | 10 mM | 0.5633 mL | 2.8163 mL | 5.6325 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： PBS Solubility: 100 mg/mL (563.25 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 6 mg/mL (33.80 mM); Clear solution
此方案可获得 ≥ 6 mg/mL (33.80 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 60.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 6 mg/mL (33.80 mM); Clear solution
此方案可获得 ≥ 6 mg/mL (33.80 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 60.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 4. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 6 mg/mL (33.80 mM); Clear solution
此方案可获得 ≥ 6 mg/mL (33.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 60.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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