iCRT3

iCRT3 is an inhibitor of β-catenin-responsive transcription (CRT).¹ It inhibits Wnt signaling in a reporter assay using HEK293 cells (IC₅₀ = 8.2 nM). It is selective for inhibition of the protein-protein interaction between β-catenin and T cell factor (Tcf) over the interaction between β-catenin and epithelial cadherin (E-cadherin) or α-catenin. iCRT3 (50 µM) inhibits neurotensin- or Wnt3a-induced increases in the proliferation of A172 and U87 glioblastoma cells.² It also reduces tumor growth in an A172 mouse xenograft model when administered at a dose of 5 mg/kg. iCRT3 (5 and 10 mg/kg) reduces plasma levels of IL-6, TNF-α, and IL-1β, as well as the general organ damage marker aspartate aminotransferase (AST) and the liver damage marker alanine transaminase (ALT) in a mouse model of cecal ligation and puncture-induced sepsis.³ It also reduces lung cell apoptosis and the severity of sepsis-induced lung injury in the same model when administered at a dose of 10 mg/kg.

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1. Gonsalves, F.C., Klein, K.O., Carson, B.B., et al. An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway. Proc. Natl. Acad. Sci. USA 108(15), 5954-5963 (2011).

2. Xiao, H., Zeng, Y., Wang, Q., et al. A novel positive feedback loop between NTSR1 and Wnt/β-Catenin contributes to tumor growth of glioblastoma. Cell. Physiol. Biochem. 43(5), 2133-2142 (2017).

3. Sharma, A., Yang, W.-L., Ochani, M., et al. Mitigation of sepsis-induced inflammatory responses and organ injury through targeting Wnt/β-catenin signaling. Sci. Rep. 7(1), 9235 (2017).