ICG 001

ICG-001 (847591-62-2) inhibits TCF/β-catenin mediated transcription by specifically blocking β-catenin/CBP interaction

(S,S)-ICG 001 is a β-turn peptidomimetic molecule inhibitor of β-catenin-Tcf-mediated transcription.

ChEBI: (6S,9aS)-6-[(4-hydroxyphenyl)methyl]-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide is a peptide.

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.

Cell permeable: yes

[1] KATAYOON H EMAMI. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected].[J]. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101 34: 12682-12687. DOI:10.1073/pnas.0404875101
[2] BEIYUN ZHOU. Interactions between β-catenin and transforming growth factor-β signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP).[J]. The Journal of Biological Chemistry, 2012, 287 10: 7026-7038. DOI:10.1074/jbc.m111.276311