Although both IWR-1 and XAV939 act as reversible Wnt pathway inhibitors and exhibit similar pharmacological effects both in vitro and in vivo, IWR-1 exerts its effect via interaction with Axin, while XAV939 binds TNKS directly.
IWR-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
iPSC-AETII cells
100 mM
7 days
IWR-1 induced the differentiation of iPSC-AETII cells to the AETI cell phenotype, significantly increasing the expression of AETI markers AQ5, T1α, and caveolin-1.
Reverse the inhibitory effects of RAL on lipid droplets and adipogenic markers
J Biomed Sci. 2019 Aug 31;26(1):62.
CD44+CD133+ Caco-2 cells
4.0-64 µM
6 days
To evaluate the anti-proliferative effects of IWR-1 on CD44+CD133+ Caco-2 cells. The results showed that IWR-1 significantly inhibited the proliferation and colony formation of CD44+CD133+ Caco-2 cells.
Int J Biol Sci. 2021 Apr 12;17(7):1644-1659.
mouse primary hepatic cells
10 μM
3 h
To investigate the effect of IWR-1 on ethanol-induced lipid accumulation in hepatic cells, results showed that IWR-1 reversed the inhibitory effect of parkin deficiency on lipid accumulation.
Cell Commun Signal. 2019 Aug 22;17(1):104.
human hepatic cancer cell line HepG2
10 μM
3 h
To investigate the effect of IWR-1 on β-catenin signaling in HepG2 cells, results showed that IWR-1 inhibited β-catenin ubiquitination.
Cell Commun Signal. 2019 Aug 22;17(1):104.
Neural Stem/Progenitor Cells (NSPCs)
1µM or 10µM
7 days
IWR-1 significantly inhibited the promoting effect of MIF on NSPC differentiation to neuron lineage
Int J Biol Sci. 2013 Nov 28;9(10):1108-20.
Neural Stem/Progenitor Cells (NSPCs)
10µM
4 days
IWR-1 significantly inhibited the proliferative effect of MIF on NSPCs
Int J Biol Sci. 2013 Nov 28;9(10):1108-20.
Porcine embryonic stem cells
1.5 µM
10 days
To evaluate the role of IWR-1 in establishing porcine embryonic stem cells, results showed that IWR-1 helps maintain self-renewal and proliferation capacity of stem cells.
Stem Cell Res Ther. 2024 Aug 7;15(1):245.
rat primary hepatocytes
10 μM
0.5 h
blocked the effect of coronarin A on β-catenin phosphorylation and inhibited gluconeogenesis
Acta Pharmacol Sin. 2023 Mar;44(3):596-609.
human lung endothelial cell (HLEC)
10 µM
24 h
restored HLEC tight-junction protein expression and inhibited prostate cancer cell transendothelial migration
Br J Cancer. 2018 May;118(11):1464-1475.
IWR-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Dbb mice
Intraperitoneal injection
5 mg/kg
Single injection
Inhibited Wnt/β-catenin signaling, attenuated aFGF-mediated endothelial protection, manifested as increased aortic endothelial cell apoptosis and increased mitochondrial ROS generation.
Redox Biol. 2021 Feb;39:101811.
Mice
Parkin knockout mice
Intraperitoneal injection
25 μM/kg
Single injection
To investigate the effect of IWR-1 on ethanol-induced hepatic lipid accumulation, results showed that IWR-1 reversed the inhibitory effect of parkin deficiency on hepatic lipid accumulation.
Cell Commun Signal. 2019 Aug 22;17(1):104.
Mice
Breast cancer xenograft model
5 mg/kg
Every other day for 2 weeks
The combination of IWR-1 with paclitaxel significantly suppressed breast cancer growth and enhanced the anti-tumor efficacy of paclitaxel.
Activity of N-terminus hexaHis-tagged human TNSK2 expressed in Escherichia coli BL21 (DE3) cells using biotinylated NAD+ as substrate after 90 mins by Western blot analysis, EC50=0.2 μM
22233320
HEK293 cells
Function assay
Displacement of IWR-PB from Axin2 in HEK293 cells by Western blot method
19125156
human DLD1 cells
Function assay
2 h
Induction of Axin2 stabilization in human DLD1 cells assessed as decreased transcription of Axin2 after 2 hrs by RT-PCR method.
19125156
human HEK293T cells
Function assay
Inhibition of beta-casein-dependent canonical Wnt3 pathway in human HEK293T cells by luciferase reporter gene assay, IC50=0.026 μM
22191557
human HT29 cells
Function assay
24 h
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, IC50=24.4 μM
24950489
human HT29 cells
25 μM
Function assay
24 h
Inhibition of Wnt signaling in human HT29 cells assessed as inhibition of beta-catenin-mediated Tcf/Lef transcriptional activity at 25 uM after 24 hrs by dual luciferase reporter gene assay relative to control in presence of GSK-3beta inhibitor LiCl
24950489
human SW480 cells
Function assay
40 to 48 h
Inhibition of tankyrase in human SW480 cells assessed as degradation of beta catenin after 40 to 48 hrs, IC50=0.25 μM
23701517
human SW480 cells
Function assay
24 h
Inhibition of tankyrase in human SW480 cells assessed as accumulation of axin2 after 24 hrs by Hoechst dye-based method
23701517
mouse L-Wnt-STF cells
Function assay
Inhibition of TNKS-2 in mouse L-Wnt-STF cells assessed as disruption of Wnt signaling after 24 hrs by luciferase reporter gene assay, IC50=0.056 μM
24527792
mouse L-Wnt-STF cells
Function assay
Inhibition of TNKS-1 in mouse L-Wnt-STF cells assessed as disruption of Wnt signaling after 24 hrs by luciferase reporter gene assay, IC50=0.131 μM
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