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IWP-2 is an inhibitor of Wnt production. IWP-2 inactivates Porcupine, a membrane-bound O-acyltransferase responsible for palmitoylating Wnt proteins, which is essential for their signaling ability and secretion. IWP-2 selectively inhibits palmitoylation of Wnt, and blocks Wnt-dependent phosphorylation of Lrp6 receptor and Dvl2, and β-catenin accumulation. IWP-2 is useful in both suppressing embryonic stem cell self-renewal and decreasing cancer cell proliferation, migration and invasion.
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Source | Front Immunol (2018). Figure 6. IWP-2 |
| Method | injected intravenously | |
| Cell Lines | C57BL/6 mice | |
| Concentrations | 20 mg/kg | |
| Incubation Time | 4.5 h | |
| Results | This view is supported by reduced percentages of IFN-γ+ liver CD3+NK1.1+ cells in mice treated with IWP-2, a small molecule inhibitor of the acyltransferase Porcupine, which plays a central role in Wnt secretion |
| Cell Experiment | |
|---|---|
| Cell lines | MKN28 cell line |
| Preparation method | Cell proliferation assay CellTiter 96 Aqueous Non-Radioactive Cell Proliferation Assay kit (Promega Corporation, Madison, WI, USA) was used. Transwell migration and invasion assay Haptotaxis chambers (8-μm pore size, Corning Costar, Cambridge, MA, USA) without or with 5 mg/ml matrigel (Sigma Aldrich) were used for migration and invasion assays, respectively. The experiments were repeated three times independently. |
| Concentrations | 0,5,10,20,50µM |
| Incubation time | 5 days |
| Animal Experiment | |
|---|---|
| Animal models | six month-old zebrafish model |
| Formulation | 0.1% DMSO |
| Dosages | 10 μM |
| Administration | in aquarium water supplemented with 10 μM IWR-1 or in 0.1% DMSO as a control |
| 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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
| Molecular Weight | 466.6 |
| Formula | C22H18N4O2S3 |
| CAS Number | 686770-61-6 |
| Purity | >99% |
| Solubility | DMSO |
| Storage | at -20°C |
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