IWP-2 is an inhibitor of Wnt processing and secretion with an IC₅₀ of 27 nM. IWP-2 targets the membrane-bound O-acyltransferase porcupine (Porcn) and thus preventing a crucial Wnt ligand palmitoylation. IWP-2 is also an ATP-competitive CK1δ inhibitor with an IC₅₀ of 40 nM for the gatekeeper mutant ^M82FCK1δ.

IWP-2 inhibits the proliferation of the investigated cell lines within the single digit μM range. IWP-2 inhibits cell proliferation in A818-6, MiaPaCa2, Panc-1, Panc-89, HT29, HEK293, SW620 and Capan cell with EC₅₀s of 8.96 μM, 1.90 μM, 2.33 μM, 3.86 μM, 4.67 μM, 2.76 μM, 1.90 μM and 2.05 μM, respectively.
Panc-1 cells are either untreated or treated with 2.33 μM IWP-2 for 48 h. In IWP-2 treated cells, the CK1δ kinase peak activity is reduced to approximately 66% residual activity compared to the activity in untreated cells, respectively. IWP-2 reduces the activity of CK1δ in Panc1 cells.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

To evaluate the efficacy of IWP-2 in vivo, 200 μL each of IWP-2-liposome or free liposome i separately injected into C57BL/6 mice intraperitoneally about 2 h before injection of a similar volume of either blue-dye-filled latex beads or E. coli DH5α. IWP-2 causes significant reduction in the uptake of blue beads as well as E. coli as assessed by CFUs in peritoneal lavage cells within 2 h. In addition, the levels of TNF-α and IL-6 in the lavage fluid of the corresponding mice are reduced by 2-4-fold compared with control values. Interestingly, IWP-2 even induces a considerable increase in secretion of the anti-inflammatory cytokine IL-10.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

To evaluate the efficacy of IWP-2 in vivo, 200 μL each of IWP-2-liposome or free liposome i separately injected into C57BL/6 mice intraperitoneally about 2 h before injection of a similar volume of either blue-dye-filled latex beads or E. coli DH5α. IWP-2 causes significant reduction in the uptake of blue beads as well as E. coli as assessed by CFUs in peritoneal lavage cells within 2 h. In addition, the levels of TNF-α and IL-6 in the lavage fluid of the corresponding mice are reduced by 2-4-fold compared with control values. Interestingly, IWP-2 even induces a considerable increase in secretion of the anti-inflammatory cytokine IL-10.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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  . García-Reyes B, et al. Discovery of Inhibitor of Wnt Production 2 (IWP-2) and Related Compounds As Selective ATP-Competitive Inhibitors of Casein Kinase 1 (CK1) δ/ε. J Med Chem. 2018 May 10;61(9):4087-4102.  [Content Brief]

  . Maiti G, et al. The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16600-5.  [Content Brief]