1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETM5441Cat. No.: HY-101761CAS No.: 1190221-43-2分式: CHClNO分量: 428.82作靶點(diǎn): PAI-1; Apoptosis作通路: Metabolic Enzyme/Protease; Apoptosis儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 300 mg/mL (69

2、9.59 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3320 mL 11.6599 mL 23.3198 mL5 mM 0.4664 mL 2.3320 mL 4.6640 mL10 mM 0.2332 mL 1.1660 mL 2.3320 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果

3、的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.83 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.83 mM); Clear solution1/2 Master of Small Molecules 您邊的抑制劑師www.Med

4、ChemEBIOLOGICAL ACTIVITY物活性 TM5441種服物可利的纖溶酶原激活物抑制劑-1 抑制劑 (PAI-1)，抑制多個(gè)癌癥細(xì)胞系的IC50 值在13.9 到 51.1 M，并誘導(dǎo)種類癌癥細(xì)胞的內(nèi)在調(diào)亡。TM5441 減弱 N-硝 -1-精氨酸甲酯誘導(dǎo)的臟壓和管衰 1 2。IC50 & Target IC50: 13.951.1 M (Tumor cell lines) 1體外研究 TM5441 dose-dependently decreases HT1080, HCT116, Daoy, MDA-MB-231 and Jurkat cells with an IC50ra

5、nging between 13.9 and 51.1 M 1.TM5441 increases caspase 3/7 activity for both HT1080 and HCT116 cells in a dose dependant manner.TM5441 increases apoptosis in HT1080 and HCT116 cells 1.TM5441 induces mitochondrial depolarization 1.In mouse proximal tubular epithelial cells, TM5441 effectively inhib

6、its PAI-1-induced mRNA expression offibrosis and inflammation markers and also reverses PAI-1-induced inhibition of plasmin activity 2.體內(nèi)研究 Oral administration of TM5441 (20 mg/kg daily) to HT1080 and HCT116 xenotransplanted mice increasestumor cell apoptosis and has a significant disruptive effect

7、on the tumor vasculature that is associated with adecrease in tumor growth and an increase in survival. The average peak plasma concentration is 11.4 Mone hour after oral administration and undetectable levels 23 hours after administration 1.TM5441 attenuates N-nitro-l-arginine methyl ester-induced

8、cardiac hypertension and vascular senescence,prolongs lifespan in klotho null mice and elicits anti-tumorigenic and anti-angiogenic activities in cancer 3.PROTOCOLCell Assay 1 HT1080, HCT116, Daoy, MDA-MB-231 and Jurkat cells are treated with 0-100 M TM5441 for 48 hours at37C. Cell viability is meas

9、ured by MTT assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: TM5275 at 50 mg/kg/day and TM5441 at 10 mg/kg/day were orally administered in control and diabeticAdministration 2 mice for 16 weeks. Mice were monitored at least once a da

10、y. At the end, blood is collected for measurementof plasma glucose and creatinine, urine for protein measurement, and kidneys for immunohistochemicalanalysis 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Placencio VR, et al. Small Molec

11、ule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity.PLoS One. 2015 Jul 24;10(7):e0133786.2. Jeong BY, et al. Novel Plasminogen Activator Inhibitor-1 Inhibitors Prevent Diabetic Kidney Injury in a Mouse Model. PLoS One. 2016Jun 3;11(6):e0157012.McePdfHei ht Caution: Product has not b