D4476
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.
D4476是一种相对特异性的和细胞穿透性的CK1和ALK5抑制剂,在体外0.1 mM ATP存在时的IC50值分别是0.3 和0.5 μM。[1]
CK1(酪蛋白激酶1)磷酸化多位点磷酸化结构域(MPDS)中靠近另一种磷酸化丝氨酸的丝氨酸残基。D4476可能是一种ATP竞争性的CK1抑制剂,其对SAPK2a/p38的抑制作用较弱并且对PKB或SGK无抑制作用。在H4IIE细胞中,FOXO1a的位点特异性磷酸化(Ser322和Ser325)分别被50和125 μM的D4476抑制,从而降低了核排斥的初始速率[1]。在Hela细胞中,CK1引起的RhoB磷酸化(Ser185)被50 μM的D4476抑制,然后RhoB依赖性肌动蛋白纤维形成随后被激活[2]。已观察到D4476治疗在HCT116细胞中产生部分的p53依赖性生长阻滞。[3]
参考文献:
1. G. Rena, J. Bain, M. Elliott and P. Cohen, EMBO Rep 2004, 5, 60-65.
2. V. Tillement, I. Lajoie-Mazenc, A. Casanova, C. Froment, M. Penary, D. Tovar, R. Marquez, B. Monsarrat, G. Favre and A. Pradines, Exp Cell Res 2008, 314, 2811-2821.
3. A. S. Huart, N. J. MacLaine, D. W. Meek and T. R. Hupp, J Biol Chem 2009, 284, 32384-32394.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 398.41 |
Cas No. | 301836-43-1 |
Formula | C23H18N4O3 |
Synonyms | Casein Kinase I Inhibitor;D 4476;D-4476 |
Solubility | insoluble in H2O; ≥19.9 mg/mL in DMSO; ≥41.5 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide |
SDF | Download SDF |
Canonical SMILES | C1COC2=C(O1)C=CC(=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5 |
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 [1,2]: | |
细胞系 |
H4IIE、Hela、HCT116细胞系 |
溶解方法 |
在DMSO中的溶解度> 19.9 mg/mL。为了获得更高浓度,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 |
H4IIE细胞: 0-150 μM孵育1小时;Hela细胞:50 μM;HCT116细胞:5– 40 μM孵育48小时 |
应用 |
在H4IIE肝癌细胞中,D4476能够特异性抑制其MPD中内源性叉头盒转录因子O1a(FOXO1a)的Ser322和Ser325磷酸化,而不影响其他部位的磷酸化。 还发现,尽管HCT116细胞经D4476处理后会造成部分p53依赖性生长停滞,但D4476诱导的p53非依赖性凋亡表明MDM2-CK1复合物在维持E2F-1抗凋亡信号通路中的关键作用。 |
References: [1] Rena G, et al. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep. 2004 Jan;5(1):60-5. [2] Huart AS, MacLaine NJ, Meek DW, Hupp TR.CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability. J Biol Chem. 2009 Nov 20;284(47):32384-94. |
质量控制和MSDS
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