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Tiplaxtinin [393105-53-8]

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Cat# HY-15253-10mg

Size : 10mg

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Tiplaxtinin is a selective and orally efficacious inhibitor of plasminogen activator inhibitor-1 (PAI-1) with IC₅₀ of 2.7 μM.

For research use only. We do not sell to patients.

Tiplaxtinin Chemical Structure

CAS No. : 393105-53-8

This product is a controlled substance and not for sale in your territory.

Based on 7 publication(s) in Google Scholar

Description

Tiplaxtinin is a selective and orally efficacious inhibitor of plasminogen activator inhibitor-1 (PAI-1) with IC₅₀ of 2.7 μM^[1].

IC₅₀ & Target

IC50: 2.7 μM (PAI-1)^[1]

In Vitro

Tiplaxtinin (PAI-039), a small-molecule inhibitor of PAI-1 activity, on the urothelial cell lines. A significant inhibition in cellular proliferation is noted in T24 cells treated with Tiplaxtinin with the documentation of a favorable IC₅₀ value of 43.7±6.3 μM and in UM-UC-14 cells 52.8±1.6 μM whereas the benign cell line, UROtsa, is noted to have a higher IC₅₀ value of 70.3±0.1 μM. Notably, IC₅₀ values of Tiplaxtinin in detached cells, 19.7±3.8 μM in T24, 44.5±6.5 μM in UM-UC-14, and 31.6±6.1 μM in UROtsa, are significantly lower than the IC₅₀ values calculated for cells cultured in the presence of Tiplaxtinin under attached conditions^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In the vena cava protocol, Tiplaxtinin (PAI-039) pretreatment significantly reduces thrombus weight at Tiplaxtinin doses of 3, 10 and 30 mg/kg. When Tiplaxtinin is dosed in a treatment paradigm 4 h after stable arterial and venous thrombosis, a significant reduction in thrombus weight is observed 24 h later at Tiplaxtinin doses of 3, 10 and 30 mg/kg^[1].
Tiplaxtinin (PAI-039) is administered by oral gavage to athymic mice bearing human bladder cancer cell line T24 xenografts and human cervical cancer HeLa cell xenografts. The subcutaneous tumor growth of both T24 and HeLa cell xenografts treated with Tiplaxtinin is markedly reduced compared with untreated controls. Specifically, at the end of the study, control T24 xenografts are noted to be 1,150±302 mm³ compared with 593±328 mm³ for T24 xenograft tumors treated with 5 mg/kg Tiplaxtinin (P<0.0001) and 627±248 mm³ for T24 xenografts treated with 20 mg/kg (P<0.0001)^[2].
Tiplaxtinin (1, 3, and 10 mg/kg) is subjected to electrolytic injury of the coronary artery. Tiplaxtinin (PAI-039) causes prolongation in time to coronary occlusion (control, 31.7±6.3 min; 3 mg/kg Tiplaxtinin, 66.0±6.4 min; 10 mg/kg, 56.7±7.4 min; n=5-6; p<0.05) and a reduced thrombus weight (control, 7.6±1.5 mg; 10 mg/kg Tiplaxtinin, 3.6±1.0 mg; p<0.05)^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

439.38

Formula

C₂₄H₁₆F₃NO₄

CAS No.

393105-53-8

Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(C(O)=O)C1=CN(CC2=CC=CC=C2)C(C1=C3)=CC=C3C4=CC=C(OC(F)(F)F)C=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (227.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : < 0.1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.69 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.69 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.69 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.78%

Select Batch:

SDS (560 KB)

COA (253 KB) LCMS (97 KB)

Handling Instructions (2659 KB)

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. [Content Brief]

[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. [Content Brief]

[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): [Content Brief]

Cell Assay ^[2]	T24, UM-UC-14, UROtsa, and HeLa cells are plated in 96-well dishes in triplicate at 1×10³ cells per well and allowed to adhere for 24 hours. Subsequently, Tiplaxtinin is added to the wells and allowed to incubate at the indicated concentrations. Cellular proliferation is determined by CellTiter-Glo Luminescent Cell Viability Assay at 24 hours, and IC₅₀ of Tiplaxtinin is determined in Graphpad Prism. Luminescence is measured using a FLUOstar OPTIMA Reader^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]^[2]	Rats^[1] Male Sprague-Dawley rats (250-350 g) are dosed orally with either vehicle or Tiplaxtinin (0.3-3 mg/kg) on the morning of the experiment, then anesthetized with sodium-pentobarbital (50 mg/kg, i.p.). A midline incision is made along the neck, and the right and left carotid arteries and jugular veins are exposed. The left jugular vein is catheterized for tPA delivery and blood sampling. The right carotid artery is cannulated with PE-60 tubing filled with 3.8% sodium citrate solution, and interfaced to a saline-filled pressure transducer for monitoring of heart rate and blood pressure. The left carotid artery is used for vascular injury induction and thrombosis. An ultrasonic flow probe is placed on the left carotid artery, and baseline blood flow is recorded. A 3-mm section of PE-60 tubing is sectioned longitudinally, and a piece of filter paper saturated with 25% FeCl₃ is inserted into the tubing. Flow is monitored in the damaged vessel during tPA infusion and for an additional 20 min afterwards. At the end of the experiment, the arterial thrombus is excised and weighed. Mice^[2] Mice bearing bladder xenografts and mice bearing cervical xenografts are divided randomly into three groups (control, 5 mg/kg of Tiplaxtinin, and 20 mg/kg of Tiplaxtinin) and treatment is initiated. Each group is composed of at least 10 mice. No toxicity or weight loss is noted in any of the treatment groups. Tiplaxtinin (100 μL diluted in corn oil) is administered via oral gavage daily (Monday-Friday) for 5 weeks. Control mice received vehicle alone on the same schedule. Tumor volumes are measured weekly with digital calipers and calculated. After 5 weeks, the mice are sacrificed, tumors resected, and analyzed by immunohistochemical staining. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. [Content Brief] [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. [Content Brief] [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): [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.2759 mL	11.3797 mL	22.7593 mL	56.8984 mL
	5 mM	0.4552 mL	2.2759 mL	4.5519 mL	11.3797 mL
	10 mM	0.2276 mL	1.1380 mL	2.2759 mL	5.6898 mL
	15 mM	0.1517 mL	0.7586 mL	1.5173 mL	3.7932 mL
	20 mM	0.1138 mL	0.5690 mL	1.1380 mL	2.8449 mL
	25 mM	0.0910 mL	0.4552 mL	0.9104 mL	2.2759 mL
	30 mM	0.0759 mL	0.3793 mL	0.7586 mL	1.8966 mL
	40 mM	0.0569 mL	0.2845 mL	0.5690 mL	1.4225 mL
	50 mM	0.0455 mL	0.2276 mL	0.4552 mL	1.1380 mL
	60 mM	0.0379 mL	0.1897 mL	0.3793 mL	0.9483 mL
	80 mM	0.0284 mL	0.1422 mL	0.2845 mL	0.7112 mL
	100 mM	0.0228 mL	0.1138 mL	0.2276 mL	0.5690 mL

Tiplaxtinin Related Classifications

Metabolic Enzyme/Protease Apoptosis
PAI-1 Apoptosis

Tiplaxtinin [393105-53-8]

Cat# HY-15253-10mg

Brand : MedChemExpress

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

Tiplaxtinin Related Classifications

Keywords:

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Tiplaxtinin [393105-53-8]

Cat# HY-15253-10mg

Brand : MedChemExpress

Tiplaxtinin Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

Tiplaxtinin Related Classifications

Keywords:

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