Tiplaxtinin (PAI-039)

Catalog No.S7922 Batch:S792202

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Technical Data

Formula

C24H16F3NO4
Molecular Weight 439.38 CAS No. 393105-53-8
Solubility (25°C)* In vitro DMSO 88 mg/mL (200.28 mM)
Ethanol 22 mg/mL (50.07 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
2%DMSO＋98%Corn oil
0.15mg/ml 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. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml 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. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Tiplaxtinin(PAI-039) is an orally efficacious and selective plasminogen activator inhibitor-1 (PAI-1) inhibitor with IC50 of 2.7 μM.
Targets
PAI-1 [1]
2.7 μM
In vitro In a panel of human bladder cell lines, PAI-1 results in the reduction of cellular proliferation, cell adhesion, and colony formation, and the induction of apoptosis and anoikis. [4]
In vivo In a rat carotid thrombosis model, Tiplaxtinin (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, Tiplaxtinin (p.o.) restores skeletal muscle regeneration. [3] In athymic mice bearing human cancer cell line T24 and HeLa xenografts, Tiplaxtinin (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]

Protocol (from reference)

Kinase Assay:[1]
  • Direct PAI-I in vitro activity assays

    The chromogenic assay is initiated by the addition of tiplaxtinin (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 tiplaxtinin, 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 the tiplaxtinin 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. Tiplaxtinin is dissolved in DMSO and diluted to a final concentration of 1-100 µM as described above. Tiplaxtinin 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 tiplaxtinin 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.
Cell Assay:[4]
  • Cell lines

    T24, UM-UC-14, UROtsa, and HeLa cells

  • Concentrations

    ~50 μM

  • Incubation Time

    24 h

  • Method

    Briefly, cell lines, 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 according to manufacturer's instructions at 24 hours, and IC50 of tiplaxtinin is determined in Graphpad Prism. Luminescence was measured using a FLUOstar OPTIMA Reader.
Animal Study:[1]
  • Animal Models

    Rat with carotid thrombosis

  • Dosages

    1 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Development, 2017, 144(8):1425-1440]

Selleck's Tiplaxtinin (PAI-039) has been cited by 15 publications

hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration [ Nat Commun, 2023, 14(1):3505] PubMed: 37311876
hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration [ Nat Commun, 2023, 14(1):3505] PubMed: 37311876
CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation [ Cell Death Dis, 2023, 14(9):614] PubMed: 37726265
CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation [ Cell Death Dis, 2023, 10.1038/s41419-023-06131-1] PubMed: 37726265
Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis [ Cell Rep Med, 2022, 3(2):100526] PubMed: 35243423
ProBDNF Dependence of LTD and Fear Extinction Learning in the Amygdala of Adult Mice [ Cereb Cortex, 2022, 32(7):1350-1364] PubMed: 34470044
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] PubMed: 33979649
Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway [ Int J Oncol, 2021, 59(2)59] PubMed: 34195849
Long-term depression at hippocampal mossy fiber-CA3 synapses involves BDNF but is not mediated by p75NTR signaling [ Sci Rep, 2021, 11(1):8535] PubMed: 33879805
PAI-1-Dependent Inactivation of SMAD4-Modulated Junction and Adhesion Complex in Obese Endometrial Cancer [ Cell Rep, 2020, 33(2):108253] PubMed: 33053339

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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