<Suppliers Price>

ICG-001

Names

[ CAS No. ]:
780757-88-2

[ Name ]:
ICG-001

[Synonym ]:
(6S,9aS)-6-(4-hydroxybenzyl)-8-naphthalen-1-ylmethyl-4,7-dioxo-hexahydro-pyrazino[1,2-a]pyrimidine-1-carboxylic acid benzylamide
(6S,9aS)-N-Benzyl-6-(4-hydroxybenzyl)-8-(1-naphthylmethyl)-4,7-dioxohexahydro-2H-pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide
(6S,9aS)-N-benzyl-6-(4-hydroxybenzyl)-8-(naphthalen-1-ylMethyl)
(6S,9aS)-N-benzyl-6-(4-hydroxybenzyl)-8-(naphthalen-1-ylmethyl)-4,7-dioxooctahydro-1H-pyrazino[1,2-a]pyrimidine-1-carboxamide
(S,S)-ICG 001
(6S,9aS)-6-(4-hydroxybenzyl)-N-benzyl-8-(naphthalen-1-ylmethyl)-4,7-dioxo-hexahydro-2H-pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide
(6S,9aS)-rel-Hexahydro-6-[(4-hydroxyphenyl)Methyl]-8-(1-naphthalenylMethyl)-4,7-dioxo-N-(phenylMethyl)-2H-pyrazino[1,2-a]pyriMidine-1(6H)-carboxaMide
(6R,9aR)-rel-Hexahydro-6-[(4-hydroxyphenyl)methyl]-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-2H-pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide
2H-Pyrazino[1,2-a]pyrimidine-1(6H)-carboxamide, hexahydro-6-[(4-hydroxyphenyl)methyl]-8-(1-naphthalenylmethyl)-4,7-dioxo-N-(phenylmethyl)-, (6S,9aS)-
ICG-001

Biological Activity

[Description]:

ICG-001 is an inhibitor of β-catenin/TCF mediated transcription. It works by specifically binding to cyclic AMP response element-binding protein with an IC50 of 3 μM.

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> Wnt
Research Areas >> Cancer

[Target]

IC50: 3 μM (CBP)


[In Vitro]

ICG-001 (5μM) inhibits leptin-induced EMT, invasion and tumorsphere formation in MCF7 cells[1]. ICG-001 can phenotypically rescue normal nerve growth factor (NGF)-induced neuronal differentiation and neurite outgrowth in the presenilin-1 mutant cells, emphasizing the importance of the TCF/β-catenin signaling pathway on neurite outgrowth and neuronal differentiation[2]. ICG-001 (25μM) treatment reduces 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 in transformed cells but not in normal colon cells, and reduces in vitro growth of colon carcinoma cells[3].

[In Vivo]

ICG-001 (5 mg/kg per day) significantly inhibits beta-catenin signaling and attenuates bleomycin-induced lung fibrosis in mice, while concurrently preserving the epithelium[2]. Administration of a water-soluble analog of ICG-001 for 9 weeks reduces the formation of colon and small intestinal polyps by 42% as effectively as the nonsteroidal antiinflammatory agent Sulindac, which has consistently demonstrated efficacy in this model. ICG-001 (150 mg/kg, i.v.) demonstrates a dramatic reduction in tumor volume over the 19-day course of treatment, with no mortality or weight loss in the SW620 nude mouse xenograft model of tumor regression[3].

[Cell Assay]

To evaluate effects of ICG-001 on α-SMA and collagen type 1 expression, RLE-6TN cells are treated with TGF-β1 (0.25 ng/mL) in the presence or absence of ICG-001 (5.0 μM). After 24 h, cells are harvested and mRNA isolated for analysis by qPCR. RNA is reverse-transcribed using SuperScript reverse transcriptase. Quantitative PCR is performed with SYBR-Green PCR using Real-Time PCR System HT7900. The amplification protocol is set as follows: 95°C denaturation for 10 min followed by 40 cycles of 15-s denaturation at 95°C, 1 min of annealing/extension, and data collection at 60°C.

[Animal admin]

Seven-week-old male C57BL/6J-ApcMin/+and WT C57BL/6J mice are treated orally for 9 weeks with ICG-001a (300 mg/kg per day) or vehicle (1% carboxymethylcellulose), once daily, six times per week. Sulindac is administered in drinking water (160 ppm, dissolved in 8 mM Na2PO4 buffer, pH 7.6). At 16 weeks, the polyp number is counted manually by using a dissecting microscope.

[References]

[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.

[4]. Liu Y, et al. ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population. J Exp Clin Cancer Res. 2017 Sep 11;36(1):125.


[Related Small Molecules]

Salinomycin | IWR-1 | Wnt-C59 | Berberine chloride hydrate | Pyrvinium pamoate | ETC-159 | BML 284 | IWP-2 | Heparan Sulfate | KYA 1797K | FH535 | SKL2001 | CCT251545 | iCRT-14 | NCB-0846

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
895.6±65.0 °C at 760 mmHg

[ Melting Point ]:
133-134ºC

[ Molecular Formula ]:
C33H32N4O4

[ Molecular Weight ]:
548.632

[ Flash Point ]:
495.4±34.3 °C

[ Exact Mass ]:
548.242371

[ PSA ]:
93.19000

[ LogP ]:
4.01

[ Vapour Pressure ]:
0.0±0.3 mmHg at 25°C

[ Index of Refraction ]:
1.722

[ Storage condition ]:
-20°C

Related Compounds