β-Catenin/Tcf Inhibitor VI, ICG-001

Cell permeable: yes

Primary Target
CREB-binding protein

Reversible: yes

Toxicity: Standard Handling (A)

A cell-permeable pyrazinopyrimidinecarboxamide that competes against β-catenin for CBP (CREB-binding protein) binding (5 to 10 µM for 24 h in SW480 and C2C12 cultures) and selectively prevents CBP- but not p300-, dependent TCF/β-catenin transcriptional regulations both in cultures in vitro (5 to 25 µM in SW480, HCT116, rat RLT-6TN, and primary human IPF lung fibroblasts; 4 to 24 h) and in mice in vivo (5 mg/kg/day via osmotic pump infusion), while not affecting CBP-dependent transcriptional activities mediated by the AP-1 or CRE complex. Selective blockage of CBP/TCF/β-catenin complex formation by ICG-001 is shown to reactivate p300//TCF/β-catenin-mediated neuronal differentiation upon NGF stimulation in PS-1 L286V mutant-expressing PC-12 cultures (cell population with neurite outgrowth = 90% and 17% of wt PS-1 control level, respectively, with or without 10 µM ICG-001) and be efficacious in alleviating bleomycin- (0,08 units/50 µL/mouse; administered intranasally; induced pulmonary fibrosis in mice (5 mg/kg/day via osmotic pump infusion; 10 d treatment starting 1 d before bleomycin induction or 21 d treatment starting d 21 post bleomycin induction).

Yan, D., et al. 2012. J. Biol. Chem.287, 8598.
Henderson, W.R. Jr, et al. 2010. Proc. Natl. Acad. Sci. USA.107, 14309.
Eguchi, M., et al. 2005. Med Chem.1, 467.
Ma, H., et al. 2005. Oncogene.24, 3619.
Teo, J.L., et al. 2005. Proc. Natl. Acad. Sci. USA.102, 12171.
Emami, K.H., et al. 2004. Proc. Natl. Acad. Sci. USA.101, 12682.

Packaged under inert gas

Use only fresh DMSO for reconstitution.

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