5.04712

β-Catenin/Tcf Inhibitor VI, ICG-001

• Szinonimák: 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
• Tapasztalati képlet (Hill-képlet): C₃₃H₃₂N₄O₄
• CAS-szám: 847591-62-2
• Molekulatömeg: 548.63
• UNSPSC kód: 12352200
• NACRES: NA.77

Tulajdonságok

• Teszt: ≥99% (HPLC)
• Minőségi szint: 100
• form: powder
• gyártó/kereskedő neve: Calbiochem^®
• tárolási körülmény: OK to freeze; protect from light
• szín: off-white
• oldhatóság: DMSO: 100 mg/mL
• tárolási hőmérséklet: 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
• Nemzetközi kémiai azonosító kulcs: HQWTUOLCGKIECB-XZWHSSHBSA-N

Leírás

Általános leírás

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.

Biokémiai/fiziológiai hatások

Cell permeable: yes

Primary Target
CREB-binding protein

Reversible: yes

Kiszerelés

Packaged under inert gas

Figyelmeztetés

Toxicity: Standard Handling (A)

Feloldás

Use only fresh DMSO for reconstitution.

Egyéb megjegyzések

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.

Jogi információk

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

Biztonsági adatok

• Tárolási osztály kódja: 11 - Combustible Solids
• WGK: WGK 3
• Lobbanási pont (F): Not applicable
• Lobbanási pont (C): Not applicable