The key mediator of Wnt signaling is the transcriptional co-activator b-catenin. In the cytoplasm, b-catenin is tightly bound to a complex that includes Axin and GSK-3b. Stimulation causes b-catenin stabilization, translocation to the nucleus and association with TCF4 to initiate transcription of responsive genes, referred to as Catenin Responsive Transcription (CRT). Virtually all Wnt-associated cancers are the result of misregulated CRT. Three inhibitors of CRT (iCRT) were identified in a screen that employed RNAi based knockdown of Axin, which stimulates CRT without affecting upstream mechanisms such as GSK activity, transduction by disheveled / frizzled, etc. These compounds are potent inhibitors of CRT reporter genes, as well as endogenous gene targets. The compounds also disrupt b-catenin-TCF4 interaction in a dose dependent manner, and cause G0/G1 arrest in colon tumor lines.
| Molecular Weight | 394.53 |
| Formula | C23H26N2O2S |
| CAS Number | 901751-47-1 |
| Form | Solid |
| Solubility (25°C) | DMSO: ≥5 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Wnt/beta-catenin Products |
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| Fz7-21
Fz7-21 (Ac-LPSDDLEFWCHVMY-NH2) is a potent peptide antagonist of FZD7 receptors , selectively binds to FZD7 CRD subclass and alters the conformation of the CRD and the architecture of its lipid-binding groove. |
| FZD7 antagonist 1
FZD7 antagonist 1 (peptide 34) is a dFz7-21 analogue. |
| NLS-StAx-h
NLS-StAx-h is a selective, cell permeable, stapled peptide Wnt signaling inhibitor with an IC50 of 1.4 μM. |
| Zamaporvint
Zamaporvint is an orally active, selective Wnt inhibitor that targets the membrane-bound o-acyltransferase porcupine and inhibits Wnt ligand palmitoylation, secretion and pathway activation. In addition, Zamaporvint displays potent antiproliferative effects in Wnt ligand-dependent colorectal and pancreatic cell lines. It can be used in cancer-related studies. |
| Foxy-5
Foxy-5, a WNT5A agonist and a mimetic peptide of WNT5A, triggers cytoplasmic free calcium signaling without affecting β-catenin activation and inhibits migration and invasion of epithelial cancer cells.Foxy-5 effectively reduces metastatic spread of prostate cancer cells with low WNT5A expression in an in situ mouse model. |
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