780757-88-2

780757-88-2 - Names and Identifiers

Name	(6S,9aS)-6-(4-Hydroxybenzyl)-8-[(naphthalen-1-yl)methyl]-4,7-dioxohexahydropyrazino[1,2-a]pyrimidine-1-carboxylic acid N-benzylamide
Synonyms	ICG-001 (S,S)-ICG 001 (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 (6S,9AS)-6-(4-HYDROXYBENZYL)-8-NAPHTHALEN-1-YLMETHYL-4,7-DIOXO-HEXAHYDRO-PYRAZINO[1,2-A]PYRIMIDINE-1-CARBOXYLIC ACID BENZYLAMIDE (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)-6-(4-Hydroxybenzyl)-8-[(naphthalen-1-yl)methyl]-4,7-dioxohexahydropyrazino[1,2-a]pyrimidine-1-carboxylic acid N-benzylamide (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 2H-PYRAZINO[1,2-A]PYRIMIDINE-1(6H)-CARBOXAMIDE,HEXAHYDRO-6-[(4-HYDROXYPHENYL)METHYL]-8-(1-NAPHTHALENYLMETHYL)-4,7-DIOXO-N-(PHENYLMETHYL)-,(6R,9AR)-REL-
CAS	780757-88-2

780757-88-2 - Physico-chemical Properties

Molecular Formula	C33H32N4O4
Molar Mass	548.63
Density	1.37
Melting Point	133-134℃
Boling Point	895.6±65.0 °C(Predicted)
Solubility	DMSO 50 mg/ml mother liquor preservation: sub-package and freeze storage to avoid repeated freezing and thawing;-20 ℃,1 month;-80 ℃,6 months (after dilution, the solution temperature is low and storage may precipitate, try to use it now) Cell experiment: Dissolve with DMSO first: dilute with culture medium then, and the dilution process is recommended to be carried out in stages to avoid excessive concentration changes leading to compound precipitation. If the compound is precipitated during the dilution process, it can be redissolved by ultrasound. During dilution, ensure that the final concentration of DMSO in the working fluid should be below 0.1% as far as possible, and the maximum should not exceed 0.5%, and set up a DMSO control group with corresponding concentration. Animal experiment: Dissolve with DMSO first: dilute with water or normal saline, etc. The dilution process is recommended to be carried out in sections to avoid excessive concentration changes leading to compound p
pKa	9.88±0.15(Predicted)
Storage Condition	-20℃
Physical and Chemical Properties	Bioactive ICG-001 (OP-724, PRI-724, CBP-beta catenin inhibitor) antagonizes Wnt/β-catenin/TCF-mediated transcription and specifically binds to the promoter binding protein (CBP) with an IC50 of 3 μM, but cannot bind to the related transcription coactivator p300. ICG-001 can induce apoptosis.
Use	ICG-001 is a potent and selective Wnt signaling modulator. ICG-001 modulates Wnt signaling and increased the expression of genes beneficial for cardiac regeneration in epicardial cells. ICG-001 binds cAMP-responsive element binding (CREB)-binding protein (CBP) to disrupt its interaction with β-catenin and inhibit CBP function as a coactivator of Wnt/β-catenin-mediated transcription. ICG-001 induces cytotoxicity of multiple myeloma cells in Wnt-independent manner. Note: Chemical structures of ICG-001 and PRI-724 look very close, but they are not the same molecule. Many vendors confused them.
Target	IC50: 3 μM (CBP)

780757-88-2 - Reference

Reference

1: Rao P, Pang M, Qiao X, Yu H, Wang H, Yang Y, Ren X, Hu M, Chen T, Cao Q, Wang Y, Khushi M, Zhang G, Wang YM, Heok P'ng C, Nankivell B, Lee VW, Alexander SI, Zheng G, Harris DC. Promotion of β-catenin/Foxo1 signaling ameliorates renal interstitial fibrosis. Lab Invest. 2019 Jun 26. doi: 10.1038/s41374-019-0276-z. [Epub ahead of print] PubMed PMID: 31243340.
2: Bocchicchio S, Tesone M, Irusta G. Convergence of Wnt and Notch signaling controls ovarian cancer cell survival. J Cell Physiol. 2019 May 13. doi: 10.1002/jcp.28775. [Epub ahead of print] PubMed PMID: 31087357.
3: Taiyab A, Holms J, West-Mays JA. β-Catenin/Smad3 Interaction Regulates Transforming Growth Factor-β-Induced Epithelial to Mesenchymal Transition in the Lens. Int J Mol Sci. 2019 Apr 27;20(9). pii: E2078. doi: 10.3390/ijms20092078. PubMed PMID: 31035577; PubMed Central PMCID: PMC6540099.
4: Cui Y, Wu X, Lin C, Zhang X, Ye L, Ren L, Chen M, Yang M, Li Y, Li M, Li J, Guan J, Song L. AKIP1 promotes early recurrence of hepatocellular carcinoma through activating the Wnt/β-catenin/CBP signaling pathway. Oncogene. 2019 Jul;38(27):5516-5529. doi: 10.1038/s41388-019-0807-5. Epub 2019 Apr 1. PubMed PMID: 30936461.
5: Chen Y, Wen H, Zhou C, Su Q, Lin Y, Xie Y, Huang Y, Qiu Q, Lin J, Huang X, Tan W, Min C, Wang C. TNF-α derived from M2 tumor-associated macrophages promotes epithelial-mesenchymal transition and cancer stemness through the Wnt/β-catenin pathway in SMMC-7721 hepatocellular carcinoma cells. Exp Cell Res. 2019 May 1;378

780757-88-2 - Preparation solution concentration reference

	1mg	5mg	10mg
1 mM	1.823 ml	9.114 ml	18.227 ml
5 mM	0.365 ml	1.823 ml	3.645 ml
10 mM	0.182 ml	0.911 ml	1.823 ml
5 mM	0.036 ml	0.182 ml	0.365 ml

Last Update：2024-01-02 23:10:35

780757-88-2 - Uses and synthesis methods

Target

Target Value

CBP

(Cell-free assay) 3 μM

in vitro studies

When the ICG-001 acts on the TOPFLASH, the IC50 is 3 μM, but it has FOPFLASH no effect on the structure of the related reporter gene containing the mutant TCF site. After treating SW480 cells with 25 μM ICG-001 for 8 hours, the stable levels of Survivin and Cyclin D1 RNA and protein were reduced, both of which were up-regulated by β-catenin. ICG-001 acts on transformed cells instead of normal colon cells, selectively inducing apoptosis and reducing the growth of colon cancer cells. ICG-001 acts on presenilin-1 mutant cells to phenotypically rescue normal nerve growth factor (NGF)-induced neuronal differentiation and neuronal axon growth, emphasizing the importance of TCF/β-catenin signaling pathway in neuronal axon growth and neuronal differentiation. The latest research shows that 5μM ICG-001 acts on MCF7 cells, inhibiting leptin-induced EMT, invasion and tumor stem cell ball formation.

In vivo studies

ICG-001 water-soluble analogs are treated for 9 weeks to reduce the formation of 42% colon and intestinal polyps. the effect is similar to that of non-steroidal anti-inflammatory agents Sulindac. Sulindac is a drug that has always been used to treat this disease model. No significant toxicity was observed throughout the treatment period. Analogues were injected intravenously at a dose of 150 mg/kg to treat SW620 nude mice tumor decline transplanted tumor model. After 19 days of treatment, the tumor volume was significantly reduced, there was no death, and there was no weight loss. ICG-001 mice were treated at a dose of 5 mg/kg per day, which significantly inhibited beta-catenin signals, reduced Bleomycin-induced pulmonary fibrosis, and protected epithelial cells.

Last Update：2024-04-09 19:04:56