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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
TM-5441 (EBP 883 and BMS-790052) is a novel orally active and potent small molecule inhibitor of plasminogen activator inhibitor-1 (PAI-1) which inhibits various tumor cell lines with IC50 values in the range of 9.7 and 60.3 μM. TM-5441 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. TM5441 protects against high-fat diet-induced obesity and adipocyte injury in mice. In mouse proximal tubular epithelial cells, TM5441 effectively inhibits PAI-1-induced mRNA expression of fibrosis and inflammation markers and also reverses PAI-1-induced inhibition of plasmin activity.
| ln Vitro |
HT1080, HCT116, Daoy, MDA-MB-231, and Jurkat cells are all dose-dependently decreased by TM5441, with an IC50 ranging from 13.9 to 51.1 μM[1]. In HT1080 and HCT116 cells, TM5441 increases caspase 3/7 activity in a dose-dependent manner. TM5441 causes HT1080 and HCT116 cells to undergo more apoptosis[1]. Mitochondrial depolarization is induced by TM5441[1]. TM5441 reverses PAI-1-induced inhibition of plasmin activity and effectively blocks fibrosis and inflammation markers' mRNA expression in mouse proximal tubular epithelial cells[2].
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| ln Vivo |
When TM5441 (20 mg/kg daily) is given orally to HT1080 and HCT116 xenotransplanted mice, it significantly disrupts the tumor vasculature and increases tumor cell apoptosis, which is linked to a reduction in tumor growth and an increase in survival. One hour after oral administration, the average peak plasma concentration is 11.4 μM, and 23 hours later, it is undetectable[1]. TM5441 extends life in klotho null mice, reduces the effects of Nω-nitro-l-arginine methyl ester-induced cardiac hypertension and vascular senescence, and has anti-tumorigenic and anti-angiogenic properties in cancer[3].
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| References |
[1]. Placencio VR, et al. Small Molecule 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. 2016 Jun 3;11(6):e0157012 |
| Molecular Formula |
C21H17CLN2O6
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| Molecular Weight |
428.82
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| CAS # |
1190221-43-2
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| Related CAS # |
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| SMILES |
O=C(O)C1=CC(Cl)=CC=C1NC(COCC(NC2=CC=CC(C3=COC=C3)=C2)=O)=O
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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 (5.83 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 (5.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3320 mL | 11.6599 mL | 23.3198 mL | |
| 5 mM | 0.4664 mL | 2.3320 mL | 4.6640 mL | |
| 10 mM | 0.2332 mL | 1.1660 mL | 2.3320 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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