TM5441 |
رقم الكتالوجGC18173
One-Click Copy Product Info
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TM5441 هو مثبط متاح حيويًا عن طريق الفم لمثبط منشط البلازمينوجين -1 (PAI-1) ، وله قيم IC50 بين 13.9 و 51.1 ميكرومتر ويؤدي إلى موت الخلايا المبرمج الجوهري في العديد من خطوط الخلايا السرطانية البشريةيخفف TM5441 ارتفاع ضغط الدم الناجم عن نيترو إل أرجينين الميثيل إستر والشيخوخة الوعائية
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1190221-43-2
Sample solution is provided at 25 µL, 10mM.
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TM5441 is an orally bioavailable inhibitor of plasminogen activator inhibitor-1 (PAI-1), has IC50 values between 13.9 and 51.1μM and induces intrinsic apoptosis in several human cancer cell lines[1]. TM5441 also exhibits anti-fibrotic and anti-tumor activities through suppression of PAI-1-mediated signaling pathways [2]. TM5441 attenuates Nω-nitro-l-arginine methyl ester-induced cardiac hypertension and vascular senescence[3].
In both HT1080 and HCT116 cells, treatment with TM5441 (25-100μM; 48h) increased Caspase 3/7 activity in a dose-dependent manner and enhanced apoptosis in both HT1080 and HCT116 cells [1].TM5441(20μM; 4h) inhibited downregulation of mitochondrial biogenesis-related genes, such as PGC-1α, mtDNA, TFAM, NRF1, and NRF2, and lipid accumulation in HepG2 cells [4]. In cardiomyocytes, TM5441(10μM; 24h) exerts its inhibitory effect on doxorubicin-induced cellular senescence by reducing the production of reactive oxygen species, inducing antioxidants such as catalase, and inhibiting stress-induced senescence [5]. In mouse proximal tubular epithelial cells, TM5441(10μM; 4h) inhibits PAI-1-induced mRNA expression of fibrosis and inflammation markers and also reverses PAI-1-induced inhibition of plasmin activity [6].
In an L-NAME-induced vascular aging model, TM5441 (20mg/kg; po; 8 weeks) prevented L-NAME-induced hypertension, cardiac hypertrophy, and periaortic fibrosis in rats. it reduced arterial p16Ink4a expression and maintained telomere length [3]. In a high-fat diet-induced nonalcoholic fatty liver disease model, early TM5441 (20mg/kg; po; 10 weeks) treatment prevented HFD-induced hepatic steatosis and reduced the expression of lipogenesis-related genes Acc1, Scd1, Cd36, and PPARγ [4]. In a mouse high-fat diet model, TM5441 (20mg/kg; po; 10 weeks) prevented high-fat diet (HFD)-induced weight gain and systemic insulin resistance. TM5441 normalized HFD-induced dysregulation of JNK and Akt phosphorylation, while also attenuating HFD-induced macrophage infiltration and increasing the expression of proinflammatory cytokines, such as inducible nitric oxide synthase[7]. In a high-fat diet model, TM5441 (15mg/kg; po; 35d) inhibited the activation of plasminogen activator-1 in mice, alleviated hypothalamic leptin resistance, and reduced high-fat diet-induced weight gain[8].
References:
[1]. Placencio V R, Ichimura A, Miyata T, et al. Small molecule inhibitors of plasminogen activator inhibitor-1 elicit anti-tumorigenic and anti-angiogenic activity[J]. PLoS One, 2015, 10(7): e0133786.
[2]. Abd Aziz Ibrahim T F, Uno T, Terada T, et al. Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand[J]. Frontiers in Immunology, 2024, 15.
[3]. Boe A E, Eren M, Murphy S B, et al. The PAI-1 antagonist TM5441 attenuates L-NAME-induced hypertension and vascular senescence[J]. Circulation, 2013, 128(21): 2318.
[4]. Lee S M, Dorotea D, Jung I, et al. TM5441, a plasminogen activator inhibitor-1 inhibitor, protects against high fat diet-induced non-alcoholic fatty liver disease[J]. Oncotarget, 2017, 8(52): 89746.
[5]. Ghosh A K, Rai R, Park K E, et al. A small molecule inhibitor of PAI-1 protects against doxorubicin-induced cellular senescence[J]. Oncotarget, 2016, 7(45): 72443.
[6]. Jeong B Y, Uddin M J, Park J H, et al. Novel plasminogen activator inhibitor-1 inhibitors prevent diabetic kidney injury in a mouse model[J]. PloS one, 2016, 11(6): e0157012. [2].
[7]. Piao L, Jung I, Huh J Y, et al. A novel plasminogen activator inhibitor‐1 inhibitor, TM5441, protects against high‐fat diet‐induced obesity and adipocyte injury in mice[J]. British journal of pharmacology, 2016, 173(17): 2622-2632.
[8]. Hosaka S, Yamada T, Takahashi K, et al. Inhibition of plasminogen activator inhibitor-1 activation suppresses high fat diet-induced weight gain via alleviation of hypothalamic leptin resistance[J]. Frontiers in Pharmacology, 2020, 11: 943.
| Cell experiment [1]: | |
Cell lines | HepG2 cells, human hepatoma cells |
Preparation Method | HepG2 cells, human hepatoma cells, were maintained in Dulbecco's Modified Eagle's Medium, supplemented with 10% fetal bovine serum, 100U/mL penicillin, 100μg/mL streptomycin, and 44mM NaHCO3 at 37°C in humidified 5% CO2. Growth arrested and synchronized cells were exposed with 50ng/mL tumor necrosis factor-α/TNF-α or 25 and 50nM mouse recombinant PAI-1 in the presence and absence of 20μM TM5441. TM5441 was added 4 hours prior to TNF-α or PAI-1 stimulation. |
Reaction Conditions | 20μM; 4h |
Applications | TM5441 inhibited downregulation of mitochondrial biogenesis-related genes ,such as PGC-1α, mtDNA, TFAM, NRF1, and NRF2, and lipid accumulation in HepG2 cells. |
| Animal experiment [1]: | |
Animal models | High fat diet (HFD)-induced NAFLD modle |
Preparation Method | 10-week-old C57BL/6J male mice were housed in a room maintained at 22±2°C with a 12h dark/12h light cycle, and fed either with normal diet (ND) or HFD. Control groups received 0.25% carboxymethyl cellulose by oral gavage; 20mg/kg TM5441 was daily administered by oral gavage on HFD mice. 10-week-treatment of TM5441 was started along with the initiation of HFD on 10-week-old mice. |
Dosage form | 20mg/kg; po; 10 weeks |
Applications | Early TM5441 treatment significantly downregulated lipogenesis-related genes (Acc1, Scd1, Cd36, and PPARγ) and upregulated lipolysis-related genes (PPARα). Hepatic steatosis was attenuated by TM5441 along with improvement of hepatic insulin sensitivity presented by decreased p-JNK along with increased p-Akt and p-GSK3β. |
References: | |
| Cas No. | 1190221-43-2 | SDF | |
| Chemical Name | 5-chloro-2-[[2-[2-[[3-(3-furanyl)phenyl]amino]-2-oxoethoxy]acetyl]amino]-benzoic acid | ||
| Canonical SMILES | O=C(COCC(NC1=CC=C(Cl)C=C1C(O)=O)=O)NC2=CC(C3=COC=C3)=CC=C2 | ||
| Formula | C21H17ClN2O6 | M.Wt | 428.8 |
| الذوبان | DMF: 33 m/ml,DMF:PBS(pH 7.2)(1:6): 0.14 mg/ml,DMSO: 20 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3321 mL | 11.6604 mL | 23.3209 mL |
| 5 mM | 466.4 μL | 2.3321 mL | 4.6642 mL |
| 10 mM | 233.2 μL | 1.166 mL | 2.3321 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 35 reference(s) in Google Scholar.)