| 產(chǎn)品描述： | Foscenvivint (ICG-001)拮抗Wnt/β-catenin/TCF介導(dǎo)的轉(zhuǎn)錄，并特異性結(jié)合到啟動(dòng)子結(jié)合蛋白（CBP)，IC50為3 μM，但不能結(jié)合到相關(guān)的轉(zhuǎn)錄共激活因子p300上。ICG-001 可誘導(dǎo)凋亡 |
| 靶點(diǎn)： |
CBP(Cell-free assay):3 μM;Apoptosis;EpigeneticReaderDomain;Wnt/beta-catenin |
| 體外研究： |
ICG-001 作用于TOPFLASH 時(shí)，IC50為3 μM，而對(duì)含突變TCF位點(diǎn)的相關(guān)報(bào)告基因結(jié)構(gòu), FOPFLASH沒有作用效果。使用25μM ICG-001處理SW480 細(xì)胞8小時(shí)后，降低Survivin和 Cyclin D1 RNA和蛋白的穩(wěn)定水平，這兩者都可通過β-catenin上調(diào)。ICG-001 作用于轉(zhuǎn)化細(xì)胞而不是正常結(jié)腸細(xì)胞，選擇性誘導(dǎo)凋亡，降低結(jié)腸癌細(xì)胞生長。ICG-001作用于presenilin-1突變細(xì)胞，可表型營救正常神經(jīng)生長因子(NGF)誘導(dǎo)的神經(jīng)元分化和神經(jīng)軸突生長，強(qiáng)調(diào)TCF/β-catenin 信號(hào)通路在神經(jīng)軸突生長和神經(jīng)元分化中的重要性。最新研究顯示 5μM ICG-001作用于MCF7細(xì)胞，抑制leptin誘導(dǎo)的EMT, 入侵和腫瘤干細(xì)胞球形成 |
| 體內(nèi)研究： |
ICG-001 水溶性類似物處理9周，降低42%結(jié)腸和小腸息肉的形成，和非甾體類抗炎試劑Sulindac效果類似，Sulindac是一貫治療這種疾病模型的藥物。在整個(gè)的處理期間觀察不到明顯的毒性。類似物按150 mg/kg 劑量靜脈注射處理SW620裸鼠腫瘤衰退移植瘤模型，處理19天，顯著降低腫瘤體積，沒有死亡，體重也沒有降低。ICG-001 每天按5 mg/kg劑量處理小鼠，顯著抑制beta-catenin信號(hào)，且降低 Bleomycin誘導(dǎo)的肺纖維化，同時(shí)保護(hù)上皮細(xì)胞 |
| 細(xì)胞實(shí)驗(yàn)： |
Cell lines: Human colon carcinoma cell lines SW480, SW620, and HCT116, normal colonic epithelial cell line CCD-841Co Concentrations: ~25 μM Incubation Time: 24 hours Method: 1. Prior to starting the assay, prepare the Apo-ONE Caspase-3/7 Reagent, and mix thoroughly. 2. For best results, empirical determination of the optimal cell number, apoptosis induction treatment and incubation period for the cell culture system may be necessary. 3. Use identical cell numbers and volumes for the assay and the negative control samples. 4. Do not mix Apo-ONE Caspase-3/7 Reagent and samples by manual pipetting. Mixing in this manner is unnecessary and may create bubbles that interfere with fluorescence readings or cross-contaminate the samples. Gentle mixing may be performed using a plate shaker. 5. Total incubation time for the assay depends upon the amount of caspase- 3/7 present in the sample. 6. The Apo-ONE Caspase-3/7 Reagent is formulated to mediate cellular lysis and support optimal caspase-3/7 activity. In rare i |
| 動(dòng)物實(shí)驗(yàn)： |
Animal Models: C57BL/6和裸鼠腫瘤模型 Dosages: 20 mg/kg Administration: 腹腔注射 |
| 參考文獻(xiàn)： |
1. 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. 2. Teo JL, et al, Specific inhibition of CBP/beta-catenin interaction rescues defects in neuronal differentiation caused by a presenilin-1 mutation. Proc Natl Acad Sci USA, 2005, 102(34), 12171-12176. 3. 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. 4. 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. 5. Huang Y, et al. Wnt/β-catenin inhibitor ICG-001 enhances the antitumor efficacy of radiotherapy by increasing radiation-induced DNA damage and improving tumor immune microenvironment in hepatocellular carcinoma. Radiother Oncol. 2021 Sep;162:34-44. |
| 溶解性： |
Soluble in DMSO |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
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 |
| 50 mM |
0.036 ml |
0.182 ml |
0.365 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險(xiǎn)品化學(xué)品經(jīng)營許可證（不帶存儲(chǔ)）
營業(yè)執(zhí)照(三證合一)
北京