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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Tiplaxtinin(PAI-039) is an orally bioactive and selective plasminogen activator inhibitor-1 (PAI-1) inhibitor with IC50 of 2.7 μM. Tiplaxtinin inhibited PAI-1 as determined by the antibody method. By use of fluorescent spectroscopy, tiplaxtinin bound to the PAI-1 mutant selectively with a Kd of 480 nM. This binding event was saturable and associated with inhibition of the protein. In a rat carotid thrombosis model, Tiplaxtinin (1 mg/kg, p.o.) increases time to occlusion and prevents the carotid blood flow reduction. In C57BL/6J mice, (1 mg/g chow) attenuates Ang II-induced aortic remodeling.
| ln Vitro |
A small chemical inhibitor of PAI-1 activity in urothelial cell lines is tiplaxtinin (PAI-039). Tiplaxtinin treatment resulted in a significant suppression of cell proliferation in T24 cells, with good IC50 values of 43.7±6.3 μM and 52.8±1.6 μM observed in UM-UC-14 cells. In contrast, the benign cell line UROtsa showed a higher IC50 value of 70.3±0.1 μM. The IC50 values of Tiplaxtinin in isolated cells were 19.7±3.8 μM in T24, 44.5±6.5 μM in UM-UC-14, and 31.6±6.1 μM in UROtsa. These values are noteworthy because they are considerably lower than the IC 50 Values that are determined for cells cultivated in the presence of Tiplaxtinin under attachment circumstances [2].
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| ln Vivo |
Tiplaxtinin (PAI-039) pretreatment considerably decreased thrombus weight in the vena cava regimen at dosages of 3, 10, and 30 mg/kg. Significant decreases in thrombus weight were noted after 24 hours at Tiplaxtinin dosages of 3, 10, and 30 mg/kg when the drug was given in a handling paradigm 4 hours after stable arterial and venous thrombosis [1]. Oral gavage of tiplaxtinin (PAI-039) was used to treat athymic mice that were xenografted with human cervical cancer HeLa cell xenografts and human bladder cancer cell line T24. Tiplaxtinin-treated T24 and HeLa cell xenografts showed a substantial reduction in subcutaneous tumor growth when compared to untreated controls. At the conclusion of the trial, the control T24 xenograft tumors were 1,150±302 mm3, but the T24 xenograft tumors treated with 5 mg were 593±328 mm3/kg tiplaxtinin (P<0.0001), and the T24 xenografts treated with 20 mg/kg (P<0.0001) had 627±248 mm3 [2]. Coronary arteries cause electrolytic injury to tilapixtinin (1, 3, and 10 mg/kg). Tiplaxtinin (PAI-039) resulted in reduced thrombus weight (control, 7.6±1.5 mg; 10 mg/kg Tiplaxtinin, 3.6±1.0 mg; p<0.05) and extended coronary occlusion (control, 31.7±6.3 minutes; 3 mg/kg Tiplaxtinin, 66.0±6.4 minutes; 10 mg/kg, 56.7±7.4 minutes; n=5–6) [3].
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| References |
[1]. Hennan JK, et al. Effect of Tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. J Thromb Haemost. 2008 Sep;6(9):1558-64.
[2]. Gomes-Giacoia E, et al. Targeting plasminogen activator inhibitor-1 inhibits angiogenesis and tumor growth in a human cancer xenograft model. Mol Cancer Ther. 2013 Dec;12(12):2697-708. [3]. Hennan JK, et al. Evaluation of PAI-039 [{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic acid], a novel plasminogen activator inhibitor-1 inhibitor, in a canine model of coronary artery thrombosis. J Pharmacol Exp Ther. 2005 Aug;314(2): |
| Molecular Formula |
C24H16F3NO4
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| Molecular Weight |
439.38
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| CAS # |
393105-53-8
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| Related CAS # |
393105-53-8 (free acid);Tiplaxtinin sodium;
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| SMILES |
FC(OC1C([H])=C([H])C(=C([H])C=1[H])C1C([H])=C([H])C2=C(C=1[H])C(C(C(=O)O[H])=O)=C([H])N2C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])(F)F
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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 (5.69 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 (5.69 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.0% Tween 80 +0.5% methylcellulose: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2759 mL | 11.3797 mL | 22.7593 mL | |
| 5 mM | 0.4552 mL | 2.2759 mL | 4.5519 mL | |
| 10 mM | 0.2276 mL | 1.1380 mL | 2.2759 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.
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