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Tiplaxtinin (PAI-039) PAI-1 inhibitor

Cat.No.S7922

PAI-039 (Tiplaxtinin) is an orally efficacious and selective plasminogen activator inhibitor-1 (PAI-1) inhibitor with IC50 of 2.7 μM.

Chemical Structure

Molecular Weight: 439.38

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.71%

99.71

Related Targets	P450 (e.g. CYP17) Dehydrogenase PDE phosphatase PPAR HSP Vitamin Transferase Carbohydrate Metabolism Mitochondrial Metabolism Casein Kinase Serine/threonin kinase Lipoxygenase Phospholipase (e.g. PLA) Retinoid Receptor DPP ACE Peroxidases Amino Acids and Derivatives Fatty Acid Synthase FXR HMG-CoA Reductase Carbonic Anhydrase Lipase Decarboxylase DHFR IDO/TDO Hydroxylase PCSK9 OXPHOS
Related Products	Notoginsenoside R1 Toddalolactone Loureirin B PAI-1 Antibody [J4H7] PAI1 Antibody [E17P19] TM5275 Sodium TM5441

Chemical Information, Storage & Stability

Molecular Weight	439.38	Formula	C₂₄H₁₆F₃NO₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	393105-53-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1=CC=C(C=C1)CN2C=C(C3=C2C=CC(=C3)C4=CC=C(C=C4)OC(F)(F)F)C(=O)C(=O)O

Solubility

In vitro
Batch:

DMSO : 88 mg/mL (200.28 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 7 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (11.38mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	2%DMSO＋98%Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.150mg/ml (0.34mM)	Taking the 1 mL working solution as an example, add 20 μL of 7.5 mg/ml clear DMSO stock solution to 980 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (11.38mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

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 ddH₂O, 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.

Mechanism of Action

Targets/IC₅₀/Ki	PAI-1 ^[1] 2.7 μM
In vitro	Tiplaxtinin (PAI-039) reduces cellular proliferation, cell adhesion, and colony formation, and induces apoptosis and anoikis in a panel of human bladder cell lines. ^[4]
Kinase Assay	Direct PAI-I in vitro activity assays
Kinase Assay	The chromogenic assay is initiated by the addition of Tiplaxtinin (PAI-039) (10 – 100 µM final concentration, maximum DMSO concentration of 0.2%) to recombinant human PAI-1 (140 nM in pH 6.6 buffer). After a 15 minute incubation at 25°C, 70 nM of recombinant human t-PA is added, and the combination of this compound, PAI-1 and tPA are incubated for an additional 30 minutes. After the second incubation, Spectrozyme tPA, is added and absorbance read at 405 nm at 0 and 60 minutes. Relative PAI-1 inhibitory activity is equal to the residual tPA activity in the tiplaxtinin / PAI-1 treatment. Control treatments include the complete inhibition of tPA by PAI-1 at the molar ratio employed (2:1), and the absence of any effect of it on t-PA alone. The immunofunctional assay is based upon the non-SDS dissociable interaction between tPA and active PAI-1. Assay plates are coated with 100 µl of a solution of t-PA (10 µg/ml in TBS), and kept at 4 °C overnight. This compound is dissolved in DMSO and diluted to a final concentration of 1-100 µM as described above. It is then incubated with human PAI-1 (50 ng/ml) for 15 minutes, and an aliquot of this solution added to the t-PA-coated plate for 1 h. The solution is aspirated from the plate, which is then washed with a buffer consisting of 0.05% Tween 20 and 0.1% BSA in TBS. This assay detects only active inhibitory PAI-1 (not latent or substrate) bound to the plate, and is quantitated using a monoclonal antibody against human PAI-1 (MA33B8). A 1000X dilution of MA33B8 is added to the plate and incubated at for one hour, aspirated and washed. A secondary antibody consisting of goat anti-mouse IgG (H+L)-AP alkaline phosphatase conjugate is added, incubated for one hour, aspirated and washed. A 100 µl aliquot of alkaline phosphatase solution is added, followed by determination of absorbance at 405 nm 60 minutes later. The quantitation of residual active PAI-1 bound to t-PA at varying concentrations of it is used to determine the IC50 by fitting the results to a logistic dose-response program, with the IC50 defined as the concentration of compound required to achieve 50% inhibition of PAI-1 activity. The assay sensitivity is 5 ng/ml of human PAI-1 as determined from a standard curve ranging from 0-100 ng/ml of human PAI-1.
In vivo	Tiplaxtinin (PAI-039) has been shown in multiple studies to exhibit various biological effects. In a rat carotid thrombosis model, it (1 mg/kg, p.o.) increases time to occlusion and prevents the carotid blood flow reduction. ^[1] In C57BL/6J mice, (1 mg/g chow) attenuates Ang II-induced aortic remodeling. ^[2] In untreated type 1 diabetic mice, this compound (p.o.) restores skeletal muscle regeneration. ^[3] In athymic mice bearing human cancer cell line T24 and HeLa xenografts, it (1 mg/kg, p.o.) reduces tumor xenograft growth, associated with a reduction in tumor angiogenesis, a reduction in cellular proliferation, and an increase in apoptosis. ^[4]
References	[1] https://pubmed.ncbi.nlm.nih.gov/15214776/ [2] https://pubmed.ncbi.nlm.nih.gov/15576638/ [3] https://pubmed.ncbi.nlm.nih.gov/21593201/ [4] https://pubmed.ncbi.nlm.nih.gov/24072883/

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