PAI-039 exhibited in vivo oral efficacy in two different models of acute arterial thrombosis. The remarkable preclinical safety and metabolic stability profiles of tiplaxtinin led to advancing the compound to clinical trials. PAI-039 exerts antithrombotic efficacy in rat models of arterial and venous vascular injury without effecting platelet aggregation. A first study demonstrates dose related effects of PAI-039 on increasing thrombus resolution and inferior vena cava blood flow without adverse effects on anti-coagulation in a rat stenosis model of venous thrombosis.
| Cell Experiment | |
|---|---|
| Cell lines | T24, UM-UC-14, UROtsa, and HeLa cells |
| Preparation method | Briefly,plating cell lines, T24, UM-UC-14, UROtsa, and HeLa cells in 96-well dishes in triplicate at 1 ×103 cells per well and allowing to adhere for 24 hours. Subsequently, adding tiplaxtinin to the wells and allowing to incubate at the indicated concentrations.Determining cellular proliferation by CellTiter-Glo Luminescent Cell Viability Assay according to manufacturer's instructions at 24 hours, and determining IC50 of tiplaxtinin in Graphpad Prism. Using a FLUOstar OPTIMA Reader to measure Luminescence . |
| Concentrations | ~50 μM |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | Rat with carotid thrombosis |
| Formulation | 2.0% Tween 80/0.5% methylcellulose |
| Dosages | 1 mg/kg |
| Administration | p.o. |
| Molecular Weight | 439.38 |
| Formula | C24H16F3NO4 |
| CAS Number | 393105-53-8 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[4] Lijnen HR, et al. Thromb Haemost. Tiplaxtinin impairs nutritionally induced obesity in mice.
| Related PAI-1 Products |
|---|
| Glutaryl-Gly-Arg-AMC
Glutaryl-Gly-Arg-AMC is a peptide substrate of urokinase plasminogen activator (uPA). |
| GGACK
GGACK (H-Glu-Gly-Arg-CMK) is an irreversible substrate-like serine protease urokinase-type plasminogen activator (uPA) inhibitor. |
| PPACK
PPACK is a plasminogen activator (rt-PA) inhibitor. |
| Anecortave acetate
Anecortave acetate is a potent ocular vascular inhibitor that inhibits angiogenic factor-induced neointima formation and also increases fibrinogen activator inhibitor 1 (PAI-1) mRNA expression.Anecortave acetate can be used in studies related to ocular neovascularization diseases. |
| SK-216
SK-216 is a plasminogen activator inhibitor-1 (PAI-1) inhibitor that acts as an anti-metastatic agent for human osteosarcoma and inhibits lung metastasis of human osteosarcoma. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
