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D4476,CK1抑制剂

CK1抑制剂

规格或纯度: ≥98%

CAS编号: 301836-43-1
分子式: C₂₃H₁₈N₄O₃
分子量: 398.41
PubChem编号: 6419753

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货号 (SKU)	包装规格	是否现货	价格	数量
D125927-10mg	10mg	现货
D125927-50mg	50mg	现货
D125927-250mg	250mg	现货

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casein kinase 1 alpha 1 Inhibitor casein kinase 1 delta Inhibitor

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基本描述

英文别名	301836-43-1\|D4476\|CK1 Inhibitor\|D 4476\|casein kinase I inhibitor\|D-4476\|Casein Kinase I Inhibitor, D4476\|4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)benzamide\|4-(4-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imida
规格或纯度	≥98%
英文名称	D4476
生化机理	D4476 is a cell-permeable triaryl substituted imidazolo compound that acts as a selective inhibitor of casein kinase 1 (CK1) and TGFβ RI (TGF-βtype-I receptor, ALK5). Weak inhibitor of Polycystin-1 (PKD1), p38? (p38α MAPK) and only weakly affects the activities of kinases, including Akt1 (PKB), SGK and GSK-3b. Suppresses the site-specific phosphorylation (Ser322 and Ser325) and nuclear exclusion of FKHR (FOXO1a) in H4IIE hepatoma cells. As an inhibitor of TGFβ RI, D4476 prevents Smad3 activation and suppresses TGFβ RI gene expression without cytotoxicity in A498 cells. In HeLa cells D4476 has been used to inhibit CK-1 phosphorylation of RhoB but not RhoA or RhoC activating RhoB dependent actin fiber formation. D4476 has been observed to block the Wnt-3a-induced phosphorylation and shift in electrophoretic migration of Dvl-1(dishevelled, Dvl).Selective cell-permeable inhibitor of casein kinase 1 (CK1) . (IC 50 values are 0.3 (CK1), 0.5 (ALK5), 9.1 (PK d 1) and 5.8 μM (p38αMAPK)). Displays selectivity over many other protein kinases.
储存温度	2-8°C储存
运输条件	冰袋运输
备注	如果有可能，您尽量在使用的当天配置溶液，并在当天使用完它。但是，如果您需要预先配制储备溶液，我们建议您将溶液等份保存在-20°C的密封小瓶中。通常，它们最多可以使用一个月。在使用前和打开样品瓶之前，我们建议您让您的产品在室温下平衡至少1小时。需要更多关于溶解度，用法和处理的建议吗？请访问我们的常见问题（FAQ）页面以获取更多详细信息。
产品介绍	D4476是可渗透入细胞的CK1δ抑制剂，IC90 <10 uM，最初是作为ALK5抑制剂A cell-permeable triaryl substituted imidazolo compound that acts as a selective inhibitor of casein kinase 1 (CK1). D4476, a cell-permeant inhibitor of CK1δ (IC90 <10 uM), originally identified as inhibitors of activin receptor-like kinase ALK5. A cell-permeable triaryl substituted imidazolo compound that acts as a selective inhibitor of casein kinase 1 (CK1).

名称和标识符

IUPAC Name	4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide
INCHI	InChI=1S/C23H18N4O3/c24-22(28)14-4-6-15(7-5-14)23-26-20(21(27-23)17-3-1-2-10-25-17)16-8-9-18-19(13-16)30-12-11-29-18/h1-10,13H,11-12H2,(H2,24,28)(H,26,27)
InChi Key	DPDZHVCKYBCJHW-UHFFFAOYSA-N
Canonical SMILES	C1COC2=C(O1)C=CC(=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5
Isomeric SMILES	C1COC2=C(O1)C=CC(=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5
WGK Germany	3
PubChem CID	6419753
分子量	398.41

数据库链接

PubChem CID	6419753
ChEMBL Ligand	CHEMBL410456
CAS Registry No.	301836-43-1

化学和物理性质

溶解性	Soluble in DMSO (~20 mg/ml), ethanol (50 mM), and 1:10 DMSO:PBS (pH 7.2) (0.1 mg/ml). Insoluble in water

安全和危险性（GHS）

WGK Germany	3
个人防护装备	Eyeshields， Gloves， type N95 (US)， type P1 (EN143) respirator filter

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参考文献

1. Rena G, Bain J, Elliott M, Cohen P. (2004) D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a.. EMBO Rep, 5 (1): (60-5). [PMID:14710188]
2. Kurihara T, Sakurai E, Toyomoto M, Kii I, Kawamoto D, Asada T, Tanabe T, Yoshimura M, Hagiwara M, Miyata A. (2014) Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors.. Mol Pain, 10 (13): (17). [PMID:24612480]
3. Kuga T et al.. (2016) Casein kinase 1 is recruited to nuclear speckles by FAM83H and SON.. Sci Rep, 6 (): (34472). [PMID:27681590]
4. Siri M et al.. (2021) Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition.. Arch Immunol Ther Exp (Warsz), 69 (): (26). [PMID:34536148]
5. Chia R et al.. (2014) Phosphorylation of LRRK2 by casein kinase 1a regulates trans-Golgi clustering via differential interaction with ARHGEF7.. Nat Commun, 5 (): (5827). [PMID:25500533]
6. Feng D et al.. (2021) Regulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation.. Sci Adv, 7 (20): (). [PMID:33990333]

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