TM5275 sodium |
| Catalog No.GC19358 |
Le TM5275 sodium est un inhibiteur de l'activateur du plasminogène (PAI-1) avec une IC50 de 6,95 μM.
Products are for research use only. Not for human use. We do not sell to patients.
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.
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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]. |
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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]. |
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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. |
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| 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+] | ||
| Formula | C28H28ClN3NaO5 | M.Wt | 544.98 |
| Solubility | DMSO : ≥ 100 mg/mL (183.49 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8349 mL | 9.1746 mL | 18.3493 mL |
| 5 mM | 367 μL | 1.8349 mL | 3.6699 mL |
| 10 mM | 183.5 μL | 917.5 μL | 1.8349 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 7 reference(s) in Google Scholar.)
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