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.
Stem Cell Reports. 2021 Jun 8;16(6):1568-1583.
Oncol Rep. 2020 Aug;44(2):577-588.
|Source||ONCOLOGY REPORTS (2020 Aug). Figure 6. IWP-2 (Abmole Bioscience, US)|
|Cell Lines||NCM460s cells|
|Concentrations||1, 10, 100 µM|
|Incubation Time||3 h|
|Results||Notably, IWP-2 also counteracted TNF-α-induced activation of the NF-κB pathway in NCM460s cells, including increased phosphorylation of IKKα/β and IκBα, decreased protein levels of IκBα and nuclear translocation of p65|
|Source||Front Immunol (2018). Figure 6. IWP-2|
|Cell Lines||C57BL/6 mice|
|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 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.|
|Incubation time||5 days|
|Animal models||six month-old zebrafish model|
|Administration||in aquarium water supplemented with 10 μM IWR-1 or in 0.1% DMSO as a control|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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.
|Solubility||DMSO 2 mg/mL
DMF 8 mg/mL
Discovery of Inhibitor of Wnt Production 2 (IWP-2) and Related Compounds As Selective ATP-Competitive Inhibitors of Casein Kinase 1 (CK1) δ/ε
Balbina Garcia-Reyes, et al. J Med Chem. 2018 May 10;61(9):4087-4102. PMID: 29630366.
The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing
George Maiti, et al. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16600-5. PMID: 23012420.
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