| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
TM5275 sodium is a novel orally active and potent small molecule inhibitor of plasminogen activator inhibitor-1 (PAI-1) which inhibits various tumor cell lines with an IC50 of 6.95 μM. TM5275 has the potential to be used to treat cancer and prevent diabetic kidney injury, because numerous studies have shown a paradoxical positive correlation between elevated levels of PAI-1 in tumors and blood of cancer patients with poor clinical outcome, also PAI-1 is increasingly recognized as a key factor in extracellular matrix (ECM) accumulation in diabetic nephropathy. TM5275 protects against high-fat diet-induced obesity and adipocyte injury in mice. In mouse proximal tubular epithelial cells, TM5275 effectively inhibits PAI-1-induced mRNA expression of fibrosis and inflammation markers and also reverses PAI-1-induced inhibition of plasmin activity.
| ln Vitro |
According to docking experiments, TM5275 attaches to PAI-1's strand 4 of the A β-sheet (s4A). TM5275 is a selective PAI-1 that does not interfere with other serpin/serine protease systems at concentrations up to 100 μM[1]. TM5275 inhibits the formation of tPA-GFP-PAI-1 high-molecular-weight complex, hence considerably extending the retention of tPA-GFP on VECs at doses of 20 and 100 μM. TM5275 accelerates the plasminogen's time-dependent buildup and the fibrin clots' disintegration on and around the tPA-GFP-expressing cells[2]. ES-2 and JHOC-9 cells treated with 70-100 μM TM5275 had reduced cell viability after 72 hours. With 100 μM TM5275, cell growth is inhibited for 48–96 hours. When treated with 100 μM TM5275, cells exhibit a substantial decrease in active PAI-1 in cell culture media as compared to the control group. It has been proposed that TM5275 may have anti-proliferative effects on ovarian cancers with elevated PAI-1 expression [3].
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| ln Vivo |
For mice and rats, TM5275 has a very low toxicity profile and a favorable pharmacokinetics profile. in models of rat thrombosis. Rats given TM5275 at doses of 10 and 50 mg/kg had considerably smaller blood clot weights (60.9±3.0 and 56.8±2.8 mg, respectively) compared to rats given vehicle treatment (72.5±2.0 mg). The antithrombotic efficacy of TM5275 (50 mg/kg) is comparable to that of the reference antithrombotic drug, ticlopidine (500 mg/kg). Following a dosage of 10 mg/kg, the plasma concentration of TM5275 reaches 17.5±5.2 μM. When TM5275 (5 mg/kg) is taken in addition to tPA (0.3 mg/kg), the antithrombotic impact of the tPA (0.3 mg/kg) is greatly increased, yielding benefits comparable to those of a high tPA dose (3 mg/kg)[1].
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| Animal Protocol |
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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.
[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 |
| Molecular Formula |
C28H27CLN3NAO5
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| Molecular Weight |
543.98
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| CAS # |
1103926-82-4
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| Related CAS # |
1103928-13-7 (free acid);1103926-82-4 (sodium);
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| SMILES |
O=C([O-])C1=CC(Cl)=CC=C1NC(COCC(N2CCN(C(C3=CC=CC=C3)C4=CC=CC=C4)CC2)=O)=O.[Na+]
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8383 mL | 9.1915 mL | 18.3830 mL | |
| 5 mM | 0.3677 mL | 1.8383 mL | 3.6766 mL | |
| 10 mM | 0.1838 mL | 0.9192 mL | 1.8383 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Decreased cell viability in cancer cells treated with TM5275 and TM5441.PLoS One.2015 Jul 24;10(7):e0133786. |
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 Treatment with TM5275 or TM5441 increases intrinsic apoptosis.PLoS One.2015 Jul 24;10(7):e0133786. |
 Increased apoptosis in cancer cells treated with TM5275 and TM5441.PLoS One.2015 Jul 24;10(7):e0133786. |
 Decreased proliferation in cancer cells treated with TM5275 and TM5441.PLoS One.2015 Jul 24;10(7):e0133786. |
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 Pre-clinical activity of TM5441 in vivo.PLoS One.2015 Jul 24;10(7):e0133786. |
 TM5441 inhibits EC branching morphogenesis.PLoS One.2015 Jul 24;10(7):e0133786. |
 TM compounds improve kidney function and morphology in STZ-induced diabetic mice.PLoS One.2016 Jun 3;11(6):e0157012. |
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 TM compounds inhibit kidney fibrosis in STZ-induced diabetic mice.PLoS One.2016 Jun 3;11(6):e0157012. |
 TM compounds inhibit kidney inflammation in STZ-induced diabetic mice.
TM compounds inhibit PAI-1-induced fibrotic and inflammatory responsesin vitro.PLoS One.2016 Jun 3;11(6):e0157012. |
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