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Usage

Uses

Used in Molecular Biology Research:
iCRT3 is used as a β-catenin inhibitor in dual luciferase assays for studying the role of β-catenin/TCF interactions and their transcriptional activity. This helps researchers understand the mechanisms of gene regulation and the influence of Wnt/β-catenin signaling pathways in various cellular processes.
Used in Pharmaceutical Development:
As a wingless/tailless (wnt) antagonist, iCRT3 is utilized to determine the essentiality of Wnt/β-catenin signaling in PROX1-mediated regulation of forkhead box protein C2 (FOXC2). This application aids in the development of potential therapeutic agents targeting Wnt/β-catenin pathways for the treatment of various diseases.
Used in Immunology:
iCRT3 is employed in the study of cytokine secretion in LPS-stimulated macrophages, providing insights into the immune response and the role of Wnt/β-catenin signaling in inflammation and other immune-related conditions.

Biochem/physiol Actions

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.