iCRT3

[Description]:

iCRT3 is an inhibitor of both Wnt and β-catenin-responsive transcription.

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> Wnt

Research Areas >> Cancer

[Target]

Wnt

[In Vitro]

iCRT3 is an inhibitor of both Wnt and β-catenin-responsive transcription. iCRT3 significantly decreases TOP Flash activity and reduces the level of NTSR1. The anti-apoptotic effects of Neurotensin (NTS) and Wnt3a can be largely abrogated by iCRT3[1]. Cells maintained long term with iCRT3 show enhanced expression of classic pluripotency genes compare with the DMSO control, whereas expression of differentiation markers and T-cell factor (TCF) target genes is concomitantly reduced[2]. Treatment with iCRT3 at doses of 12.5, 25, 50, and 75 μM decreases TNF-α levels by 14.7%, 18.5%, 44.9% and 61.3%, respectively. With iCRT3 treatment, IκB levels are increased in a dose-dependent manner compare to the vehicle[3].

[In Vivo]

The tumor growth rates are markedly retarded by iCRT3 treatment. Consistently, the tumor-suppressive role of iCRT3 is accompanied with a reduction in Ki67 index, a proliferation marker[1]. The IL-6 levels in the 10 mg/kg iCRT3 treatment group are 82.9% lower than those in the vehicle group. IL-1β levels are undetectable in the sham but reach 371 pg/mL in septic mice and are down by 30.2% and 53.2%, respectively, with 5 and 10 mg/kg iCRT3. With iCRT3 treatment at doses of 5 and 10 mg/kg, AST levels in these septic mice are 15.4% and 44.2% lower, respectively, than those in the vehicle-treated mice. After treatment with 10 mg/kg iCRT3, lung morphology is improved with much reduced microscopic deterioration, compare to the vehicle group. The number of apoptotic cells in the lung tissues of the iCRT3-treated mice is significantly reduced by 92.7% in comparison with the vehicle group[3].

[Cell Assay]

Cells are seeded into 96-well plates to a density of 5×103 cells per well and incubated in the culture medium with iCRT3 for an additional 48 h. Cell viability and cell apoptosis assays are carried out using a Cell Counting kit-8 and a Caspase-Glo 3/7 assay kit according to the manufacturer’s instructions, respectively[1].

[Animal admin]

NOD-SCID BALB/c mice are inoculated subcutaneously in the right back with 2×106 A172 cells. The growth of the primary tumors is recorded every 4 days. iCRT3 (5 mg/kg) is diluted in PBS i.p. triweekly when tumors grow to ~200 mm3. The control mice are treated with blank PBS containing 5% (v/v) DMSO. Tumor volume is evaluated with the following formula: volume=tumor length×width2/2. The mice are sacrificed 24 days after pharmaceutical treatment. The tumors are resected and embedded in paraffin, and the Ki67 staining is analyzed by immunohistochemistry[1].

[References]

[1]. Xiao H, et al. A Novel Positive Feedback Loop Between NTSR1 and Wnt/β-Catenin Contributes to Tumor Growth of Glioblastoma. Cell Physiol Biochem. 2017 Oct 24;43(5):2133-2142.

[2]. Chatterjee SS, et al. Inhibition of β-catenin-TCF1 interaction delays differentiation of mouse embryonic stem cells. J Cell Biol. 2015 Oct 12;211(1):39-51.

[3]. Sharma A, et al. Mitigation of sepsis-induced inflammatory responses and organ injury through targeting Wnt/β-catenin signaling. doi: 10.1038/s41598-017-08711-6.

[Related Small Molecules]

ICG-001 | Salinomycin | IWR-1 | Wnt-C59 | Berberine chloride hydrate | Pyrvinium pamoate | ETC-159 | BML 284 | IWP-2 | Heparan Sulfate | KYA 1797K | FH535 | SKL2001 | CCT251545 | iCRT-14

[ Molecular Formula ]:
C₂₃H₂₆N₂O₂S

[ Molecular Weight ]:
394.53000

[ Exact Mass ]:
394.17100

[ PSA ]:
80.43000

[ LogP ]:
5.19540

[ Storage condition ]:
-20℃

[ Symbol ]:

GHS05, GHS07

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H315-H318-H335

[ Precautionary Statements ]:
P261-P280-P305 + P351 + P338

[ RIDADR ]:
NONH for all modes of transport

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