5.04712

β-Catenin/Tcf Inhibitor VI, ICG-001

• 別名: 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
• 実験式（ヒル表記法）: C₃₃H₃₂N₄O₄
• CAS番号: 847591-62-2
• 分子量: 548.63
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• アッセイ: ≥99% (HPLC)
• 品質水準: 100
• 形状: powder
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: off-white
• 溶解性: DMSO: 100 mg/mL
• 保管温度: 2-8°C
• 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
• InChI Key: HQWTUOLCGKIECB-XZWHSSHBSA-N

詳細

詳細

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).

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.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
CREB-binding protein

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

Use only fresh DMSO for reconstitution.

その他情報

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.

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable