ICG-001

生物活性

ICG-001拮抗Wnt/β-catenin/TCF介导的转录，能特异性结合到元件结合蛋白（CBP），IC50为3 μM，但不能结合到相关的转录共激活因子p300上。ICG-001 作用于TOPFLASH 时，IC50为3 μM，而对含突变TCF位点的相关报告基因结构, FOPFLASH没有作用效果。使用25μM ICG-001处理SW480 细胞8小时后，降低Survivin和 Cyclin D1 RNA和蛋白的稳定水平，这两者都可通过β-catenin上调。ICG-001 作用于转化细胞而不是正常结肠细胞，选择性诱导凋亡，降低结肠癌细胞生长。

实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）

细胞实验
细胞系	NCI-H929, U266, MM1S, and RPMI-8226
方法	Cells were treated with various concentrations of ICG-001 for 24 hours. 3-[4, 5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) dye (Sigma) was added for the last 4 hours of incubation. Insoluble formazan complexes were pelleted and solubilized with DMSO, and absorbance was measured at 540 nm using a Benchmark Plus microplate spectrophotometer (Bio-Rad, Hercules, CA). The IC50 values were calculated using CalcuSyn software (Biosoft, Cambridge, UK). Each experimental condition was done in triplicate and repeated at least once.
浓度	0-50 µ M
处理时间	24 h

动物实验
动物模型	MM tumors were established in SCID-beige mice by subcutaneous inoculation of 1x107 MM RPMI-8226 cells in the right flank
配制	Solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide (Sigma-Aldrich) and 6% Solutol (Sigma-Aldrich).
剂量	100 mg/kg ICG-001 twice a day
给药处理	administered intraperitoneally

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。

化学数据

储备液配制

以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.8227 mL	9.1136 mL	18.2272 mL
5 mM	0.3645 mL	1.8227 mL	3.6454 mL
10 mM	0.1823 mL	0.9114 mL	1.8227 mL

使用AbMole产品发表的文献

• 

  J Biomed Sci. 2020 Jan 13;27(1):5.

  Involvement of collagen XVII in pluripotency gene expression and metabolic reprogramming of lung cancer stem cells.
  ICG-001购买自AbMole

• 

  Onco Targets Ther. 2019 Aug 30;12:7067-7077.

  Upregulation of SHIP2 participates in the development of breast cancer via promoting Wnt/β-catenin signaling.
  ICG-001购买自AbMole

• 

  Oncogene. 2015 Sep 17.

  Oncogenic KRAS signalling promotes the Wnt/β-catenin pathway through LRP6 in colorectal cancer.
  ICG-001购买自AbMole

客户产品验证及相关生物数据

	数据来源	Oncogene (2014). Figure 1. ICG-001 was purchased from AbMole BioSciences (Kowloon, Hong Kong, China)
	方法	microscopy images
	细胞系	IEC-6 caMEK
	浓度	7.5 µ M
	处理时间	36 h
	实验结果	"The caMEK-transformed cells showed a partial reversion to an epithelial morphology after treatment of caMEK-transformed cells with ICG-001, a small-molecule antagonist of β-catenin/ TCF-mediated transcription."

参考文献

Interactions between β-catenin and transforming growth factor-β signaling pathways mediate epithelial-mesenchymal transition and are dependent on the transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP).
Zhou B, et al. J Biol Chem. 2012 Mar 2;287(10):7026-38. PMID: 22241478.

Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis.
Henderson WR Jr, et al. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14309-14. PMID: 20660310.

A small molecule inhibitor of beta-catenin/CREB-binding protein transcription.
Emami KH, et al. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12682-7. PMID: 15314234.