TM5275 sodium

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

TM5275 是纤溶酶原激活物抑制剂 1 (PAI-1) 的抑制剂。

TM5275 is an inhibitor of plasminogen activator inhibitor 1 (PAI-1).

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?μM) does not interfere with other serpin/serine protease systems. TM5275 at concentrations of 20 and 100 μM 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. Cell viability at 72 h treatment is decreased with 70-100 μM TM5275 in ES-2 and JHOC-9 cells. From 48 h up to 96 h, cell growth is suppressed with 100 μM TM5275.Active PAI-1 in cell culture media is significantly decreased in cells treated with 100 μM TM5275 compared to control treatment. TM5275 is suggested to exert anti-proliferative effects in ovarian cancer with high PAI-1 expression.

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).

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Apoptosis

NF-κB

PAI-1

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1103926-82-4

543.98

C28H27ClN3NaO5

>98% (HPLC)

DMSO : ≥ 100 mg/mL; 183.49 mM

[Na+].[O-]C(=O)c4cc(Cl)ccc4NC(=O)COCC(=O)N1CCN(CC1)C(c2ccccc2)c3ccccc3

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(-20℃)

With Ice Pack

≥ 2 years