Biochem/physiol Actions

Reversible: yes

Cell permeable: yes

Primary TargetCREB-binding protein

General description

A cell-permeable pyrazinopyrimidinecarboxamide that competes against β-catenin for CBP (CREB-binding protein) binding and selectively prevents CBP- but not p300-, dependent TCF/β-catenin transcriptional regulations both in cultures in vitro (5 to 25 µM) 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. Shown to reactivate p300//TCF/β-catenin-mediated neuronal differentiation upon NGF stimulation in PS-1 L286V mutant-expressing PC-12 cultures and be efficacious in alleviating bleomycin- (0,08 units/50 µL/mouse; administered intranasally; Cat. No. 203401) induced pulmonary fibrosis in mice.

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; Cat. No. 203401) 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).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

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.

Packaging

Packaged under inert gas

Reconstitution

Use only fresh DMSO for reconstitution.

Warning

Toxicity: Standard Handling (A)