IWR-1 (Synonyms: endo-IWR 1; IWR-1-endo)

Cat. No.: HY-12238G: Data Sheet Handling Instructions
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IWR-1 (IWR-1-endo) (GMP) is the IWR-1 (HY-12238) produced by using GMP guidelines. GMP small molecules work appropriately as an auxiliary reagent for cell therapy manufacture. 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.

For research use only. We do not sell to patients.

IWR-1 Chemical Structure

CAS No. : 1127442-82-3

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Biological Activity
Purity & Documentation
References
Customer Review

Description

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	[PMID: 24950489]
HEK-293T	IC₅₀	26 nM Compound: 1, IWR-1	Inhibition of beta-casein-dependent canonical Wnt3 pathway in human HEK293T cells by luciferase reporter gene assay Inhibition of beta-casein-dependent canonical Wnt3 pathway in human HEK293T cells by luciferase reporter gene assay	[PMID: 22191557]
HEK293	IC₅₀	136 μM Compound: 1, IWR1	Inhibition of Tankyrase in human HEK293 cells assessed as inhibition of Wnt pathway by Wnt3a-induced STF assay Inhibition of Tankyrase in human HEK293 cells assessed as inhibition of Wnt pathway by Wnt3a-induced STF assay	[PMID: 23316926]
HT-29	GI₅₀	> 100 μM Compound: IWR1	Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay	[PMID: 24950489]
HT-29	IC₅₀	24.4 μM Compound: IWR1	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	[PMID: 24950489]
HT-29	IC₅₀	9.52 μM Compound: IWR-1	Cytotoxicity against human HT-29 cells assessed as cell viability at 1.563 to 50 uM measured after 72 hrs by plate reader method Cytotoxicity against human HT-29 cells assessed as cell viability at 1.563 to 50 uM measured after 72 hrs by plate reader method	[PMID: 34062253]
HepG2	GI₅₀	95.4 μM Compound: IWR1	Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay	[PMID: 24950489]
LoVo	GI₅₀	63.1 μM Compound: IWR1	Antiproliferative activity against human LoVo cells after 72 hrs by MTT assay Antiproliferative activity against human LoVo cells after 72 hrs by MTT assay	[PMID: 24950489]
SW480	EC₅₀	2.5 μM Compound: 1, IWR1	Inhibition of tankyrase in human SW480 cells assessed as accumulation of axin2 after 24 hrs by Hoechst dye-based method Inhibition of tankyrase in human SW480 cells assessed as accumulation of axin2 after 24 hrs by Hoechst dye-based method	[PMID: 23701517]
SW480	IC₅₀	0.25 μM Compound: 1, IWR1	Inhibition of tankyrase in human SW480 cells assessed as degradation of beta catenin after 40 to 48 hrs Inhibition of tankyrase in human SW480 cells assessed as degradation of beta catenin after 40 to 48 hrs	[PMID: 23701517]

In Vitro

IWR-1 (GMP) is cytotoxic for osteosarcoma cancer stem-like cells (CSCs)^[1].
IWR-1 (GMP) suppresses cell migration, invasion, and matrix metalloproteinase activities of colorectal cancer cell lines^[2].
IWR-1 (GMP) (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 (GMP) (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 (GMP) (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 (GMP) (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 (GMP) (5-50 μM, 24-48 h) decreases the proliferation of HCT116 cells in a dose- and time-dependent manner^[2].
IWR-1 (GMP) (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.

Cell Viability Assay^[1]

Cell Line:	MG-63 and MNNG-HOS spheres and parent cells
Concentration:	2.5, 5, 7.5, 10 μM
Incubation Time:	48 and 96 h
Result:	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).

Western Blot Analysis^[1]

Cell Line:	MG-63 and MNNG-HOS spheres and parent cells
Concentration:	10 μM
Incubation Time:	96 h
Result:	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.

RT-PCR^[1]

Cell Line:	MG-63 and MNNG-HOS spheres and parent cells
Concentration:	10 μM
Incubation Time:	96 h
Result:	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.

Western Blot Analysis^[2]

Cell Line:	HCT116 cells
Concentration:	5, 10, 20, 50 μM
Incubation Time:	0, 4, 8, 24, 48 h
Result:	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.

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 (GMP) (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.

Molecular Weight

409.44

Formula

C₂₅H₁₉N₃O₃

CAS No.

1127442-82-3

SMILES

O=C(NC1=C2N=CC=CC2=CC=C1)C3=CC=C(N(C([C@]4([H])[C@](C5)([H])C=C[C@]5([H])[C@]64[H])=O)C6=O)C=C3

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Sara R. Martins-Neves, et al., IWR-1, a tankyrase inhibitor, attenuates Wnt/β-catenin signaling in cancer stem-like cells and inhibits in vivo the growth of a subcutaneous human osteosarcoma xenograft, Cancer Letters, Volume 414, 2018, Pages 1-15, ISSN 0304-3835. [Content Brief]

[2]. Lee SC, et al., IWR-1 inhibits epithelial-mesenchymal transition of colorectal cancer cells through suppressing Wnt/β-catenin signaling as well as survivin expression. Oncotarget. 2015 Sep 29;6(29):27146-59.

[3]. Wang, W. M., et al., IWR-1 attenuates the promotional effect of IL-36γ in a mouse model of psoriasis. BMC immunology, 25(1), 78. [Content Brief]

[4]. Chen, B., Dodge, M.E., Tang, W., et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat. Chem. Biol. 5(2), 100-107 (2009). [Content Brief]

IWR-1 Related Classifications

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Help & FAQs

Do most proteins show cross-species activity?
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.

Keywords:

IWR-1 (GMP)1127442-82-3endo-IWR 1 (GMP)IWR-1-endo (GMP)OrganoidWntInhibitorinhibitorinhibit

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