IWR-1 induces cell differentiation. (A) NB4 and (B) HL-60 cells are treated with 0 (DMSO), 5 and 10 μM IWR-1 for three days, and the expression of β-catenin and differentiation marker CD11b is assessed by western blotting.
SCAPs are cultured with modified neural differentiation medium for the indicated time periods. The neuron-like cells in control group, SFRP2 over-expressed group and 10 uM IWR1-endo treated group are positive for βIII-tubulin (red) expression by using immunofluorescence staining.
IWR-1 (IWR-1-endo) is a tankyrase inhibitor targeting Wnt/β-catenin (IC50 = 180 nM). IWR-1 compromises critical steps of the canonical Wnt signaling, namely translocation of β-catenin to the nucleus and subsequent TCF/LEF activation and expression of Wnt/β-catenin downstream targets. IWR-1 promotes β-catenin phosphorylation by promoting stability of Axin-scaffolded destruction complexes. IWR-1 can be studied in research for anti-tumor purposes, and diseases such as osteosarcoma, colorectal cancer and psoriasis[1][2][4].
IC50 & Target
IC50: 180 nM (Wnt)
细胞效力 (Cellular Effect)
Cell Line
Type
Value
Description
References
A549
GI50
> 100 μM
Compound: IWR1
Antiproliferative activity against human A549 cells after 72 hrs by MTT assay
Antiproliferative activity against human A549 cells after 72 hrs by MTT assay
Inhibition of Wnt signaling in human HT29 cells assessed as inhibition of beta-catenin-mediated Tcf/Lef transcriptional activity after 24 hrs by dual luciferase reporter gene assay relative to control
Inhibition of Wnt signaling in human HT29 cells assessed as inhibition of beta-catenin-mediated Tcf/Lef transcriptional activity after 24 hrs by dual luciferase reporter gene assay relative to control
Led to an upregulation of Bak and a downregulation of Bcl-2 (key proteins involved in mitochondrial-dependent apoptosis), which contributes to a Bak/Bcl-2 ratio >1 that prone the cells to undergo apoptosis.
Resulted in a higher β-catenin nuclear/cytoplasmic ratio in spheres, indicating an increased Wnt/β-catenin pathway activation in osteosarcoma spheres.
Stabilized Axin2 protein levels.
Diminished the protein expression levels of Cyclin D1 in both parental cells and spheres.
Led to an upregulation of Bak and a downregulation of Bcl-2 (key proteins involved in mitochondrial-dependent apoptosis), which contributes to a Bak/Bcl-2 ratio >1 that prone the cells to undergo apoptosis.
Results in a higher β-catenin nuclear/cytoplasmic ratio in spheres, indicating an increased Wnt/β-catenin pathway activation in osteosarcoma spheres.
Stabilized Axin2 protein levels.
Diminished the protein expression levels of Cyclin D1 in both parental cells and spheres.
Reduced cell viability when concentration is higher than 5 μM.
Elicited more than 70% reduction of cell viability in spheres derived from the two cell lines at 96 h with 10 μM.
Had minimal effect on parental cells since the Wnt/β-catenin signaling is absent in these cells.
Increased the susceptibility of spheres towards Doxorubicin (HY-15142) when treated in combination with increasing concentrations of Doxorubicin (0.01-100 μM).
Increased the levels of the epithelial marker E-cadherin whilst decreased the mesenchymal markers N-cadherin, Vimentin, and Snail dose- and time-dependently.
Inhibited the EMT process in HCT116 cells effectively.
Decreased β-catenin expression and inhibited the EMT-like expressional changes whereby decreasing N-cadherin and Snail and increasing E-cadherin expressions, even in the presence of TNF-α (HY-P1860) (10 ng/mL for 24 h)-induced EMT stimulation.
Decreased the phosphorylation of Akt in a concentration- and time-dependent manner.
Decreased the surviving expression in a concentration- and time-dependent manner, thereby promoting tumor proliferation directly or indirectly through regulating cancer cell homeostasis.
Reduced MMP activities only when surviving was suppressed.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Immunocompromised nude mice (6-week old female Swiss nude) were injected sub-cutaneously the pGL4-transfected MNNG-HOS cells (2×106 cells/100 mL PBS)[1]
Dosage:
5 mg/kg
Administration:
Intratumorally, each 2 d for 12 d
Result:
Resulted in slower tumor growth rate and reduction in tumor size by 73% and 71% in comparison to control and to Doxorubicin-treated (8 mg/kg, i.p., each 4 d for 12 d) groups.
Enhanced the therapeutic efficacy of Doxorubicin shown by a greater reduction of tumor burden at the end of the treatment in opposite to Doxorubicin alone.
Animal Model:
Balb/c mice (aged 6-8 weeks) with shaven back and treated with a daily topical dose of IMQ cream[3]
Dosage:
10 mg/kg
Administration:
Subcutaneous injection (s.c.) on days 1, 3, 5
Result:
Increased epidermal thickening with keratinocyte thickness.
Significantly diminished the effect of IMQ on hyperplasia in the IMQ+IWR-1 group.
Ameliorated the pathological changes in IL-36γ-induced psoriasiform skin lesion.
Reversed IL-36γ-mediated upregulation of inflammatory factors (IL-17 A and IFN-γ) in psoriatic lesions.
Reversed IL-36γ-mediated upregulation of β-catenin and DKK1 expression.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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