TM5275 sodium salt

Cas No.:	1103926-82-4
Chemical Name:	2-[2-[2-(4-Benzhydrylpiperazin-1-yl)-2-oxoethoxy]acetamido]-5-chlorobenzoic acid sodium salt 5-Chloro--[[2-[2-[4-(diphenylmethyl)-1-piperazinyl]-2-oxoethoxy]acetyl]amino]-benzoic acid sodium salt
Synonyms:	TM 5275，TM-5275
SMILES:	C1CN(CCN1C(C2=CC=CC=C2)C3=CC=CC=C3)C(=O)COCC(=O)NC4=C(C=C(C=C4)Cl)C(=O)[O-].[Na+]
Formula:	C28H27ClN3NaO5
M.Wt:	543.97
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	TM5275 sodium is a plasminogen activator inhibitor (PAI-1) with an IC50 of 6.95 μM.
In Vivo:	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].
In Vitro:	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[1]. 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[2]. 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[3].