ICG 001
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
ICG001是Wnt/β-catenin信号通路的小分子抑制剂,与β-catenin竞争结合CBP(CREB-binding protein)而非转录共激活因子p300,从而抑制TCF/β-catenin介导的转录,IC50值为3 μM [1]。ICG001可用于特异性评估CBP/β-catenin在WNT信号和细胞生理学中的作用。
据报道,ICG001可以选择性地抑制结肠癌细胞(SW480和HCT-116)的生长,但对正常的结肠上皮细胞(CCD-841Co)不起作用。在结肠癌异种移植的Min小鼠和裸鼠中,ICG001也是有效的[1]。ICG-001可以有效的抑制培养中的GBM干细胞的生长。在实验模型中,ICG-001选择性地抑制Wnt/β-catenin/CBP信号通路,从而逆转肺纤维化和改善实验性皮肤纤维化 [2,3]。ICG001目前处于临床试验阶段,用于治疗结肠癌和白血病。
参考文献:
[1]Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, Ha JR, Kahn M. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12682-7.
[2]Henderson WR Jr1, Chi EY, Ye X, Nguyen C, Tien YT, Zhou B, Borok Z, Knight DA, Kahn M. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14.
[3]Beyer C, Reichert H, Akan H, Mallano T, Schramm A, Dees C, Palumbo-Zerr K, Lin NY, Distler A, Gelse K, Varga J, Distler O, Schett G, Distler JH. Blockade of canonical Wnt signalling ameliorates experimental dermal fibrosis. Ann Rheum Dis. 2013 Jul;72(7):1255-8.
- 1. Mingxin Wen, Hui Ren, et al. "CT45A1 promotes the metastasis of osteosarcoma cells in vitro and in vivo through β-catenin." Cell Death Dis. 2021 Jun 25;12(7):650. PMID: 34172717
- 2. Duan Y, Qiu Y, et al. "Deletion of FHL2 in fibroblasts attenuates fibroblasts activation and kidney fibrosis via restraining TGF-β1-induced Wnt/β-catenin signaling." J Mol Med (Berl). 2020; 98 (2): 291–307. PMID: 31927599
- 3. Fatima I, El-Ayachi I, et al. "Simultaneous Multi-Organ Metastases from Chemo-Resistant Triple-Negative Breast Cancer Are Prevented by Interfering with WNT-Signaling." Cancers (Basel). 2019 Dec 17; 11 (12). pii: E2039. PMID: 31861131
- 4. Wasnik S, Lakhan R, et al. "Cyclooxygenase 2 augments osteoblastic but suppresses chondrocytic differentiation of CD90(+) skeletal stem cells in fracture sites." Sci Adv. 2019 Jul 31; 5 (7): eaaw2108. PMID: 31392271
- 5. Zhou J, Toh SH, et al. "A loss-of-function genetic screening reveals synergistic targeting of AKT/mTOR and WTN/β-catenin pathways for treatment of AML with high PRL-3 phosphatase." J Hematol Oncol. 2018 Mar 7; 11 (1): 36. PMID: 29514683
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 548.63 |
Cas No. | 847591-62-2 |
Formula | C33H32N4O4 |
Solubility | ≥27.43 mg/mL in DMSO; insoluble in H2O; ≥35.47 mg/mL in EtOH with ultrasonic |
Chemical Name | (6S,9aS)-N-benzyl-6-[(4-hydroxyphenyl)methyl]-8-(naphthalen-1-ylmethyl)-4,7-dioxo-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide |
SDF | Download SDF |
Canonical SMILES | C1CN(C2CN(C(=O)C(N2C1=O)CC3=CC=C(C=C3)O)CC4=CC=CC5=CC=CC=C54)C(=O)NCC6=CC=CC=C6 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
大鼠心外膜细胞 |
溶解方法 |
在DMSO中的溶解度 >10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
10 μM;24 h |
应用 |
用DMSO、ICG-001或IQ1处理大鼠EMCs,并进行免疫共沉淀(co-IP)试验。在DMSO处理的对照细胞中,所有的β连环蛋白与CBP相关联。IQ1对β连环蛋白共激活因子的使用影响很小。正如预期,ICG-001减少β连环蛋白/ CBP的相互作用,同时伴随β连环蛋白/ p300相互作用的增加。 |
动物实验[1]: | |
动物模型 |
雌性Sprague-Dawley大鼠 |
剂量 |
50 mg/kg/day;皮下注射 |
应用 |
通过手术对大鼠左冠状动脉进行永久闭塞,从而诱导左心室区域缺血性损伤。自手术当天开始,用ICG-001处理10天,手术后4周(最后一次ICG-001处理后20天)通过血管造影评估左心室射血分数,作为心脏收缩功能的指标。ICG-001显著提高8.4%的射血分数(从46.2±1.7%到54.6±3.4%,P < 0.05)。这些数据表明,在大鼠心肌梗死后,ICG-001显著改善心脏收缩功能。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Sasaki T, Hwang H, Nguyen C, et al. The small molecule Wnt signaling modulator ICG-001 improves contractile function in chronically infarcted rat myocardium. PloS one, 2013, 8(9): e75010. |
描述 | ICG-001拮抗Wnt/β-catenin/TCF介导的转录,并特异性与启动子结合蛋白(CBP)相结合,IC50值为3 μM。 | |||||
靶点 | CBP | |||||
IC50 | 3 μM |
质量控制和MSDS
- 批次: