TM5275 sodium
目录号 : GC19358
A PAI-1 inhibitor
Cas No.:1103926-82-4
Sample solution is provided at 25 µL, 10mM.
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TM5275 sodium is a plasminogen activator inhibitor (PAI-1) with an IC50 of 6.95 uM.
Docking studies shows that TM5275 binds to strand 4 of the A β-sheet (s4A) position of PAI-1. TM5275 is a selective PAI-1 and (up to 100 uM) does not interfere with other serpin/serine protease systems[1]. TM5275 at concentrations of 20 and 100 uM significantly prolongs the retention of tPA-GFP on VECs by inhibiting tPA-GFP-PAI-1 high-molecular-weight complex formation. TM5275 enhances the time-dependent accumulation of plasminogen as well as the dissolution of fibrin clots on and around the tPA-GFP-expressing cells[2]. Cell viability at 72 h treatment is decreased with 70-100 uM TM5275 in ES-2 and JHOC-9 cells. From 48 h up to 96 h, cell growth is suppressed with 100 uM TM5275. Active PAI-1 in cell culture media is significantly decreased in cells treated with 100 uM TM5275 compared to control treatment. TM5275 is suggested to exert anti-proliferative effects in ovarian cancer with high PAI-1 expression[3].
TM5275 exhibits a favorable pharmacokinetics profile and very low toxicity to mice and rats. In rat thrombosis models. Blood clot weights are significantly lower in rats administered 10 and 50 mg/kg of TM5275 (60.9±3.0 and 56.8±2.8 mg, respectively) than in vehicle-treated rats (72.5±2.0 mg). The antithrombotic effectiveness of TM5275 (50 mg/kg) is equivalent to that of ticlopidine (500 mg/kg), a reference antithrombotic compound. Plasma concentration of TM5275 reaches 17.5±5.2 uM after a dose of 10 mg/kg. TM5275 (5 mg/kg) combined with tPA (0.3 mg/kg) significantly enhances the antithrombotic effect of tPA (0.3 mg/kg) alone and provides a benefit similar to that of a high tPA dose (3 mg/kg)[1].
References:
[1]. Izuhara Y, et al. A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates. J Cereb Blood Flow Metab. 2010 May;30(5):904-12.
[2]. Yasui H, et al. TM5275 prolongs secreted tissue plasminogen activator retention and enhances fibrinolysis on vascular endothelial cells. Thromb Res. 2013 Jul;132(1):100-5.
[3]. Mashiko S, et al. Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer. Cancer Biol Ther. 2015;16(2):253-60.
Kinase experiment: | TM5275 exhibits a favorable pharmacokinetics profile and very low toxicity to mice and rats. In rat thrombosis models. Blood clot weights are significantly lower in rats administered 10 and 50 mg/kg of TM5275 (60.9±3.0 and 56.8±2.8 mg, respectively) than in vehicle-treated rats (72.5±2.0 mg). The antithrombotic effectiveness of TM5275 (50 mg/kg) is equivalent to that of ticlopidine (500 mg/kg), a reference antithrombotic compound. Plasma concentration of TM5275 reaches 17.5±5.2 μM after a dose of 10 mg/kg. TM5275 (5 mg/kg) combined with tPA (0.3 mg/kg) significantly enhances the antithrombotic effect of tPA (0.3 mg/kg) alone and provides a benefit similar to that of a high tPA dose (3 mg/kg)[1]. |
Cell experiment: | ES2 cells are treated with DMSO (control) or 100 μM TM5275 for the indicated periods (24, 48, 72, 96 hour). Cell growth is determined by CellTiter-Glo assay[1]. |
Animal experiment: | Rats: Thrombus formation in arteriovenous shunts is achieved in male CD rats. Either TM5275 (10 and 50 mg/kg, n=9) or ticlopidine (500 mg/kg, n=6), suspended in 0.5% CMC solution, is administered orally by gavage 90 mins before the study. Control rats are administered only a 0.5% CMC solution (n=10). Blood is allowed to circulate through the shunt for 30 mins. The wet weight of the thrombus covering the silk thread is eventually measured[1]. Mice: TM5275 is administered orally by gavage to male ICR mice (50 mg/kg). Heparinized blood samples are collected from the vein before (0 h) and 1, 2, 6, and 24 h after oral drug administration. Plasma drug concentration is determined on a reverse-phase high-performance liquid chromatography[1]. |
References: [1]. Izuhara Y, et al. A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates. J Cereb Blood Flow Metab. 2010 May;30(5):904-12. | |
| Cas No. | 1103926-82-4 | SDF | |
| Canonical SMILES | O=C(O)C1=CC(Cl)=CC=C1NC(COCC(N2CCN(C(C3=CC=CC=C3)C4=CC=CC=C4)CC2)=O)=O.[Na+] | ||
| 分子式 | C28H28ClN3NaO5 | 分子量 | 544.98 |
| 溶解度 | DMSO : ≥ 100 mg/mL (183.49 mM) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8349 mL | 9.1746 mL | 18.3493 mL |
| 5 mM | 0.367 mL | 1.8349 mL | 3.6699 mL |
| 10 mM | 0.1835 mL | 0.9175 mL | 1.8349 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet