5.04712

β-Catenin/Tcf Inhibitor VI, ICG-001

• Sinónimos: β-Catenin/Tcf Inhibitor VI, ICG-001, (6 S,9a S)-Hexahydro-6-((4-hydroxyphenyl)methyl)-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-2H-pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide, (6 S)-N-Benzyl-6-(p-hydroxyphenylmethyl)-8-(1-naphthylmethyl)-4,7-dioxohexahydro-2H-, (6S,9aS)-Hexahydro-6-((4-hydroxyphenyl)methyl)-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-2H-pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide, (6S)-N-Benzyl-6-(p-hydroxyphenylmethyl)-8-(1-naphthylmethyl)-4,7-dioxohexahydro-2H-pyra
• Fórmula empírica (notación de Hill): C₃₃H₃₂N₄O₄
• Número de CAS: 847591-62-2
• Peso molecular: 548.63
• Número MDL: MFCD21362415
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• Ensayo: ≥99% (HPLC)
• Nivel de calidad: 100
• Formulario: powder
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: off-white
• solubilidad: DMSO: 100 mg/mL
• temp. de almacenamiento: 2-8°C
• cadena SMILES: N21[C@@H](N(CCC2=O)C(=O)NCc6ccccc6)CN(C(=O)[C@@H]1Cc5ccc(cc5)O)Cc3c4c(ccc3)cccc4
• InChI: 1S/C33H32N4O4/c38-27-15-13-23(14-16-27)19-29-32(40)35(21-26-11-6-10-25-9-4-5-12-28(25)26)22-30-36(18-17-31(39)37(29)30)33(41)34-20-24-7-2-1-3-8-24/h1-16,29-30,38H,17-22H2,(H,34,41)/t29-,30+/m0/s1
• Clave InChI: HQWTUOLCGKIECB-XZWHSSHBSA-N

Descripción

Descripción general

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).

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
CREB-binding protein

Reversible: yes

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Use only fresh DMSO for reconstitution.

Otras notas

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.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3
• Punto de inflamabilidad (°F): Not applicable
• Punto de inflamabilidad (°C): Not applicable