Tiplaxtinin(PAI-039)
(Synonyms: ALPHA-氧代-1-(苯基甲基)-5-[4-(三氟甲氧基)苯基]-1H-吲哚-3-乙酸,PAI-039; Tiplasinin) 目录号 : GC12387
A PAI-1 inhibitor
Cas No.:393105-53-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | T24, UM-UC-14, UROtsa, and HeLa cells are plated in 96-well dishes in triplicate at 1×103 cells per well and allowed to adhere for 24 hours. Subsequently, Tiplaxtinin is added to the wells and allowed to incubate at the indicated concentrations. Cellular proliferation is determined by CellTiter-Glo Luminescent Cell Viability Assay at 24 hours, and IC50 of Tiplaxtinin is determined in Graphpad Prism. Luminescence is measured using a FLUOstar OPTIMA Reader[2]. |
Animal experiment: | Rats[1] Male Sprague-Dawley rats (250-350 g) are dosed orally with either vehicle or Tiplaxtinin (0.3-3 mg/kg) on the morning of the experiment, then anesthetized with sodium-pentobarbital (50 mg/kg, i.p.). A midline incision is made along the neck, and the right and left carotid arteries and jugular veins are exposed. The left jugular vein is catheterized for tPA delivery and blood sampling. The right carotid artery is cannulated with PE-60 tubing filled with 3.8% sodium citrate solution, and interfaced to a saline-filled pressure transducer for monitoring of heart rate and blood pressure. The left carotid artery is used for vascular injury induction and thrombosis. An ultrasonic flow probe is placed on the left carotid artery, and baseline blood flow is recorded. A 3-mm section of PE-60 tubing is sectioned longitudinally, and a piece of filter paper saturated with 25% FeCl3 is inserted into the tubing. Flow is monitored in the damaged vessel during tPA infusion and for an additional 20 min afterwards. At the end of the experiment, the arterial thrombus is excised and weighed. Mice[2] Mice bearing bladder xenografts and mice bearing cervical xenografts are divided randomly into three groups (control, 5 mg/kg of Tiplaxtinin, and 20 mg/kg of Tiplaxtinin) and treatment is initiated. Each group is composed of at least 10 mice. No toxicity or weight loss is noted in any of the treatment groups. Tiplaxtinin (100 μL diluted in corn oil) is administered via oral gavage daily (Monday-Friday) for 5 weeks. Control mice received vehicle alone on the same schedule. Tumor volumes are measured weekly with digital calipers and calculated. After 5 weeks, the mice are sacrificed, tumors resected, and analyzed by immunohistochemical staining. |
References: [1]. Hennan JK, et al. Effect of Tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. J Thromb Haemost. 2008 Sep;6(9):1558-64. | |
Description:
IC50: 2.7 μM
Plasminogen activator inhibitor-1 (PAI-1) is the most important physiologic regulator of the plasminogen activation system through its inhibition of its target serine proteases, tissue plasminogen activator, and urokinase plasminogen activator. Significant elevations of PAI-1 lead to stabilization of arterial and venous thrombi, which contribute respectively to coronary arterial occlusion in postmyocardial infarction and venous thrombosis following postoperative recovery from orthopedic surgery. Tiplaxtinin (PAI-039) is a novel, orally efficacious inhibitor of PAI-1.
In vitro: Tiplaxtinin inhibited PAI-1 as determined by the antibody method. By use of fluorescent spectroscopy, tiplaxtinin bound to the PAI-1 mutant selectively with a Kd of 480 nM. This binding event was saturable and associated with inhibition of the protein [1].
In vivo: In the rat model of carotid thrombosis, oral administration of tiplaxtinin at 1 mg/kg increased time to occlusion and prevented the carotid blood flow reduction when compared to the vehicle group. All of the vehicle control rats exhibited thrombosis with an average time to occlusion of 11 min and a complete reduction of 100% carotid flow. Conversely, those rats receiving tiplaxtinin at 1 mg/kg po exhibited an average time to occlusion of >50 min and a carotid blood flow reduction of approximately 50% [1].
Clinical trial: Up to now, tiplaxtinin is still in the preclinical development stage.
Reference:
[1] Elokdah H, Abou-Gharbia M, Hennan JK, McFarlane G, Mugford CP, Krishnamurthy G, Crandall DL. Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization. J Med Chem. 2004 Jul 1;47(14):3491-4.
| Cas No. | 393105-53-8 | SDF | |
| 别名 | ALPHA-氧代-1-(苯基甲基)-5-[4-(三氟甲氧基)苯基]-1H-吲哚-3-乙酸,PAI-039; Tiplasinin | ||
| 化学名 | 2-(1-benzyl-5-(4-(trifluoromethoxy)phenyl)-1H-indol-3-yl)-2-oxoacetic acid | ||
| Canonical SMILES | FC(F)(OC1=CC=C(C2=CC(C(C(C(O)=O)=O)=CN3CC4=CC=CC=C4)=C3C=C2)C=C1)F | ||
| 分子式 | C24H16F3NO4 | 分子量 | 439.38 |
| 溶解度 | ≥ 17.6mg/mL in DMSO | 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 | 2.2759 mL | 11.3797 mL | 22.7593 mL |
| 5 mM | 0.4552 mL | 2.2759 mL | 4.5519 mL |
| 10 mM | 0.2276 mL | 1.138 mL | 2.2759 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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