ICG 001 [β-catenin; CBP; TCF Inhibitor]

ICG-001 antagonizes Wnt / β-catenin / TCF-mediated transcription and specifically binds CREB binding protein (CBP) with IC50 of 3μM. No effect on β-catenin / p300 interaction. In colon cancer cell lines (SW480 and HCT-116 cells), it showed growth inhibitory effect; ICG-001 selectively induced apoptosis in transformed cells, but did not induce apoptosis in normal colon cells, thereby reducing colon cancer cells Growth in vitro. ICG-001 can phenotypically rescue neuronal differentiation and neurite outgrowth in normal nerve growth factor (NGF) -induced presenilin-1 mutant cells, emphasizing the TCF / β-catenin signaling pathway in neurite outgrowth and neurons The importance of differentiation.

(6S,9aS)-Hexahydro-6-[(4-hydroxyphenyl)methyl]-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-2H-pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide

Inhibitor

Neurological Disorders

ICG-001 (5 μM) inhibits leptin-induced EMT, invasion and tumor sphere formation in MCF7 cells [1]. ICG-001 can rescue the neuronal differentiation and neurite outgrowth of normal nerve growth factor (NGF) -induced presenilin-1 mutant cells, revealing the effect of TCF / β-catenin signaling pathway on neurite outgrowth and neuronal differentiation [2]. ICG-001 (25μM) treatment can reduce the steady-state levels of Survivin and Cyclin D1 RNA and protein in SW480 cells, both of which can be up-regulated by β-catenin. ICG-001 selectively induces apoptosis of transformed cells without inducing apoptosis of normal colon cells and reduces the growth of colon cancer cells in vitro [3].

[1]. Yan D, et al, Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. J Biol Chem, 2012, 287(11), 8598-8612.
[2]. Henderson WR Jr, et al, Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci USA, 2010, 107(32), 14309-14314.
[3]. Emami KH, et al. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci USA, 2004, 101(34), 12682-12687.

ICG-001 (5 mg / kg per day) can significantly inhibit β-catenin signaling in mice. ICG-001 treatment (9 weeks) can effectively reduce the formation of colon and small intestine polyps by 42% in animal models. ICG-001 (150 mg / kg, i.v.) showed a significant reduction in tumor volume during 19 days of treatment, and no death or weight loss was observed in the SW620 nude mouse xenograft model [3].

[1]. Yan D, et al, Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. J Biol Chem, 2012, 287(11), 8598-8612.
[2]. Henderson WR Jr, et al, Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci USA, 2010, 107(32), 14309-14314.
[3]. Emami KH, et al. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci USA, 2004, 101(34), 12682-12687.

548.6

Powder

C33H32N4O4

Synthetic

O=C(NCC1=CC=CC=C1)N2CCC(N([C@@]2(CN(C3=O)CC4=C5C=CC=CC5=CC=C4)[H])[C@H]3CC6=CC=C(C=C6)O)=O

Soluble to 100 mM in DMSO and to 50 mM in ethanol

3 μM

780757-88-2

≥99%

-20°C

Room Temperature

For obtaining a higher solubility, please warm the tube at 37 °C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

For research use only

β-catenin; CBP; TCF

Catenin β-1, also known as β-catenin, is a protein encoded by the CTNNB1 gene in humans.
β-catenin is a dual-function protein involved in the regulation of cell adhesion and gene transcription. In humans, the CTNNB1 protein is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo. β-catenin is a subunit of cadherin complex, which plays a role in intracellular signal transduction in Wnt signaling pathway. It is a member of the catenin protein family and is homologous to γ-catenin (also known as plakoglobin). β-catenin is widely expressed in many tissues. In the myocardium, β-catenin is localized to the adhesive connection in the inserted intervertebral disc structure, which is essential for the electrical and mechanical coupling between adjacent cardiomyocytes.
The mutation and overexpression of β-catenin are related to many cancers, including hepatocellular carcinoma, colorectal cancer, lung cancer, malignant breast tumors, ovarian cancer and endometrial cancer. Changes in the location and expression levels of β-catenin are associated with various forms of heart disease, including dilated cardiomyopathy. β-catenin is regulated and destroyed by β-catenin destruction complex, especially adenomatous polyposis (APC) protein encoded by tumor-suppressing APC gene. Therefore, the genetic mutation of the APC gene is also closely related to cancer, especially colorectal cancer caused by familial adenomatous polyposis (FAP).