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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 induces increase in Axin protein levels accompanied by elevated levels of β-catenin. IWR-1 can be studied in research for anti-tumor purposes, and diseases such as osteosarcoma, colorectal cancer and psoriasis.
For research use only. We do not sell to patients.
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 induces increase in Axin protein levels accompanied by elevated levels of β-catenin. 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)
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
IWR-1 is cytotoxic for osteosarcoma cancer stem-like cells (CSCs)[1].
IWR-1 suppresses cell migration, invasion, and matrix metalloproteinase activities of colorectal cancer cell lines[2].
IWR-1 (2.5-10 μM, 48-96 h) is effective in reducing spheres’ viability in a concentration- and time- dependent manner in parental and spheres from MG-63 and MNNG-HOS cell lines[1].
IWR-1 (10 μM, 96 h) increases the number of TUNEL-positive cells, reaching 4.65- and 15.83-fold differences relative to control at 96 h and promoted the activation of caspases 3/7 reaching 2.15- and 1.27-fold in MG-63 and MNNG-HOS spheres[1].
IWR-1 (10 μM, 48 h) induces a cell cycle arrest in the G2/M phase in spheres derived from MG-63 and MNNG-HOS cell lines and increases the percentage of cells in the S phase slightly[1].
IWR-1 (10 μM, 48 h) inhibits secondary sphere-forming efficacy by approximately 53% and 55% of the first-generation 7-day old spheres in MG-6t4 and MNNG-HOS cells[1].
IWR-1 (5-50 μM, 24-48 h) decreases the proliferation of HCT116 cells in a dose- and time-dependent manner[2].
IWR-1 (5-50 μM, 24-48 h) inhibits TNF-α-stimulated migration in HCT116 and HT29 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
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.
Inhibited EMT in the mRNA levels under the TNF-α-induced EMT stimulation.
In Vivo
IWR-1 (5 mg/kg, intratumorally, each 2 d for 12 d) induces a marked inhibition of tumor growth in osteosarcoma mouse model[1].
IWR-1 (10 mg/kg, s.c., on days 1, 3, 5) ameliorates IL-36γ (2 μg/mouse on days 1, 3, 5)-mediated exacerbation of psoriatic skin lesions in an Imiquimod (IMQ) (HY-B0180)-induced psoriasis-like mice model[3].
MedChemExpress (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.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (122.12 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.4424 mL
12.2118 mL
24.4236 mL
5 mM
0.4885 mL
2.4424 mL
4.8847 mL
10 mM
0.2442 mL
1.2212 mL
2.4424 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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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