TMPA 是一种具有高亲和力的Nur77拮抗剂，与Nur77结合导致LKB1在细胞质中释放和穿梭，以激活AMPKα。TMPA 能有效地降低血糖，减轻 II 型 db/db、高脂饮食和链脲霉素诱导的糖尿病小鼠的胰岛素抵抗。TMPA 能减少人类 T 细胞的 RICD，也可用于癌症和 T 细胞凋亡失调的研究。
| 生物活性 | TMPA is a high-affinityNur77antagonist that binds toNur77leading to the release and shuttling ofLKB1in the cytoplasm to activateAMPKα. TMPA effectively lowers blood glucose and attenuatesinsulinresistance in type II db/db, high-fat diet and streptozotocin-induced diabetic mice. TMPA reduces RICD (restimulation-induced cell death) in human T cells, can also be used in studies ofcancerand T-cellapoptosisdysregulation[1][2]. |
体外研究
(In Vitro) | TMPA (5, 10, 20, 40, 80 μM; 6 h or 10 μM; 0.5, 1, 3, 6, 12, 24, 36, 48 h) antagonizes the Nur77-LKB1 interaction in a dose- and time-dependent manner in hepatic LO2 cells[1].
TMPA (10 μM; 6 h) enhances the LKB1-AMPKα interaction but decreases the LKB1-Nur77 interaction under physio logical conditions in Lo2 cells[1].
TMPA binds directly to LBD in specific conformation[1].
TMPA (10, 20 μM; 6 h) induces LKB1 nuclear export to activate AMPKα in Lo2 cells[1].
TMPA (10, 50, 100 μM; 4 h) impairs human T-cell RICD (restimulation-induced cell death)[2].
Cell Viability Assay[2] | Cell Line: | T cells | | Concentration: | 10, 50, 100 μM | | Incubation Time: | 4 h | | Result: | Significantly reduced T-cell RICD in a dose-dependent manner. |
Western Blot Analysis[1] | Cell Line: | Hepatic LO2 cells | | Concentration: | 10, 20 μM | | Incubation Time: | 6 h | | Result: | Led to an increase of LKB1 phosphorylation at Ser428. |
Western Blot Analysis[1] | Cell Line: | Hepatic LO2 cells | | Concentration: | 5, 10, 20, 40, 80 μM | | Incubation Time: | 6 h | | Result: | Increased the amount of phosphorylation of AmPKα in a dose- and time-dependent manner.
Rescued the LKB1-AmPKα interaction by reducing the nur77-lKb1 interaction when at 10 μM. |
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体内研究
(In Vivo) | TMPA (50 mg/kg; i.p.; single daily for 19 days) is capable of lowering blood glucose and improving glucose tolerance in type II diabetic mice[1].
| Animal Model: | Male C57BL/KsJ-Leprdb/Leprdb(db/db) mice (10-week-old; type II diabetic model)[1]. | | Dosage: | 50 mg/kg | | Administration: | Intraperitoneal injection; single daily for 19 days. | | Result: | Significantly reduced blood glucose at day 7 and persisted during the remainder of the test.
Increased the amount of phosphorylated AMPKα in the liver of mice. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(262.83 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.6283 mL | 13.1413 mL | 26.2826 mL | | 5 mM | 0.5257 mL | 2.6283 mL | 5.2565 mL | | 10 mM | 0.2628 mL | 1.3141 mL | 2.6283 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-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
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此方案可获得 ≥ 2.5 mg/mL (6.57 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.57 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.57 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 25.0 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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