TMPA
目录号 : GC30015
TMPA是一种Nur77拮抗剂，可阻止Nur77与LKB1的结合，并刺激LKB1向胞质转运及磷酸化。
Cas No.:1258275-73-8
Sample solution is provided at 25 µL, 10mM.
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TMPA, a Nur77 antagonist, prevents the binding of Nur77 and LKB1 as well as stimulates LKB1 transport to the cytosol and phosphorylation [1]. The binding of TMPA to Nur77 decreases the stability of Nur77-LKB1 complex by inducing an open-close motion of Nur77 and thereby facilitates the solvation of the interface region[2]. TMPA has been widely used in diabetic mouse models to regulate blood glucose levels[3].
In vitro, TMPA treatment at 10μM for 1 hour increased the phosphorylation of AMPK in hepatic L02 cells [4]. Treatment of mouse bone marrow-derived mast cells (BMMCs) with 10μM TMPA for 6 hours increased phosphorylation of LKB1 and AMPK and concomitantly reduced IgE/Ag-induced degranulation and eicosanoid production, which inhibited FcεRI-mediated mast cell signaling[5]. Treatment with 10μM TMPA for 18h significantly increased TNFα-induced IL-6 production in HeLa cells[6]. Pretreatment of HepG2 cells with 10μM TMPA for 6 hours reduced lipid accumulation after free fatty acid (FFA) stimulation[7].
In vivo, Intraperitoneal injection of TMPA (50mg/kg/day) once daily for 19 days significantly reduced insulin levels, lowered blood glucose, and improved glucose tolerance in diabetic mice[8].
References:
[1] Wu L, Chen L. Characteristics of Nur77 and its ligands as potential anticancer compounds[J]. Molecular medicine reports, 2018, 18(6): 4793-4801.
[2] Rungsung I, Rajagopalan M, Ramaswamy A. Molecular dynamics study of TMPA mediated dissociation of Nur77-LKB1 complex[J]. Computational Biology and Chemistry, 2018, 76: 67-78.
[3] Safe S. Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators[J]. Histology and histopathology, 2023, 39(5): 543.
[4] Li L, Liu Y, Chen H, et al. Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation[J]. Nature chemical biology, 2015, 11(5): 339-346.
[5] Jin F, Li X, Deng Y, et al. The orphan nuclear receptor NR4A1 promotes FcεRI‐stimulated mast cell activation and anaphylaxis by counteracting the inhibitory LKB1/AMPK axis[J]. Allergy, 2019, 74(6): 1145-1156.
[6] Huang B, Pei H Z, Chang H W, et al. The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase 2α[J]. Scientific reports, 2018, 8(1): 13895.
[7] Wang X, Li G, Guo C, et al. Ethyl 2-[2, 3, 4-Trimethoxy-6-(1-Octanoyl) Phenyl] acetate (Tmpa) ameliorates lipid accumulation by disturbing the combination of Lkb1 with Nur77 and activating the ampk pathway in Hepg2 cells and mice primary hepatocytes[J]. Diabetes, Metabolic Syndrome and Obesity, 2021: 4165-4177.
[8] Zhan Y, Chen Y, Zhang Q, et al. The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK[J]. Nature chemical biology, 2012, 8(11): 897-904.
TMPA是一种Nur77拮抗剂，可阻止Nur77与LKB1的结合，并刺激LKB1向胞质转运及磷酸化[1]。TMPA通过诱导Nur77的开放-闭合运动降低Nur77-LKB1复合物的稳定性，从而促进界面区域的溶剂[2]。TMPA已广泛应用于糖尿病小鼠模型中调节血糖水平[3]。
在体外，10μM的TMPA处理肝L02细胞1小时可增加AMPK磷酸化[4]。10μM的TMPA处理小鼠骨髓来源肥大细胞（BMMCs）6小时能提高LKB1和AMPK磷酸化水平，同时减少IgE/抗原诱导的脱颗粒和类二十烷酸产生，并抑制FcεRI介导的肥大细胞信号传导[5]。10μM的TMPA处理HeLa细胞18小时可显著增强TNFα诱导的IL-6产生[6]。10μM的TMPA预处理HepG2细胞6小时能减少游离脂肪酸（FFA）刺激后的脂质积累[7]。
在体内，糖尿病小鼠每日腹腔注射TMPA（50mg/kg/day；持续19天）可显著降低胰岛素水平、血糖并改善葡萄糖耐量[8]。
| Cell experiment [1]: | |
Cell lines | L02 cells |
Preparation Method | The human liver cell line (L02) was cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS), 100 units of penicillin, and 100μg/ml streptomycin. Cells were treated with 10μM TMPA for 1h, and the amount of AMPKα phosphorylation was determined by western blot. |
Reaction Conditions | 10μM; 1h |
Applications | TMPA increased the phosphorylation of AMPK in hepatic L02 cells. |
| Animal experiment [2]: | |
Animal models | Male C57BL/KsJ-Leprdb/Leprdb (db/db) mice |
Preparation Method | Male C57BL/KsJ-Leprdb/Leprdb (db/db) mice were randomly divided into three groups. One group of mice was injected intraperitoneally with TMPA once daily at a dose of 50mg/kg for 19 days. The remaining groups were injected with metformin (250mg/kg) or vehicle (DMSO) as positive and negative controls. Mice were fasted for 18h prior to measurement of blood glucose. Mouse blood glucose was measured every 4 days. After 19 days of treatment, mice were intraperitoneally injected with D-glucose (1g/kg) for a glucose tolerance test. |
Dosage form | 50mg/kg/day for 19 days; tail vein injection |
Applications | TMPA treatment reduced blood glucose and improved glucose tolerance in diabetic mice. |
References: | |
| Cas No. | 1258275-73-8 | SDF | |
| Canonical SMILES | COC1=C(CC(OCC)=O)C(C(CCCCCCC)=O)=CC(OC)=C1OC | ||
| 分子式 | C21H32O6 | 分子量 | 380.48 |
| 溶解度 | DMSO : ≥ 100 mg/mL (262.83 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6283 mL | 13.1413 mL | 26.2826 mL |
| 5 mM | 525.7 μL | 2.6283 mL | 5.2565 mL |
| 10 mM | 262.8 μL | 1.3141 mL | 2.6283 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.50%
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