DC Chemicals Limited
China
Product Name: D4476 (D-4476)
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Purity: 98.0%
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Dayang Chem (Hangzhou) Co., Ltd.
China
Product Name: D4476
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Purity: 98.0%
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301836-43-1

301836-43-1 structure

301836-43-1 structure

Name: D4476
Chemical Name: 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide
CAS Number: 301836-43-1
Molecular Formula: C₂₃H₁₈N₄O₃
Molecular Weight: 398.414
Catalog: Signaling Pathways Autophagy Autophagy
Create Date: 2018-12-31 16:39:16
Modify Date: 2024-01-10 09:32:13
D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC50 value of 0.3 μM in vitro.

Name	4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide
Synonyms	4-(4-(2,3-Dihydrobenzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide 4-[4-(2,3-Dihydro-1,4-benzodioxin-6-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl]benzamide Benzamide, 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]- CK1 Inhibitor 4-[4-(2,3-Dihydro-1,4-benzodioxin-6-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide Casein Kinase I Inhibitor D4476

Description	D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC50 value of 0.3 μM in vitro.
Related Catalog	Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> Cell Cycle/DNA Damage >> Casein Kinase Signaling Pathways >> Stem Cell/Wnt >> Casein Kinase Research Areas >> Cancer
Target	CK1:0.3 μM (IC50)
In Vitro	D4476 is a potent and rather selective inhibitor of CK1 in vitro and in cells. In H4IIE hepatoma cells, D4476 specifically inhibits the phosphorylation of endogenous forkhead box transcription factor O1a (FOXO1a) on Ser322 and Ser325 within its MPD, without affecting the phosphorylation of other sites. CK1δ assayed at 0.1 mM ATP using a phosphorylated peptide TFRPRTSpSNASTIS corresponding to residues 312–325 of FOXO1a is inhibited with an IC50 value of 0.3 μM. The IC50 value for CK1δ decreases progressively as the concentration of ATP is lowered, indicating that D4476 is an ATP-competitive inhibitor of CK1. CK1[1].
Cell Assay	D4476 is used for inhibition of Csnk1a1. D4476 is added to leukemia cells cultured in 96-well plates (5,000 cells per well) in medium supplemented with 10 ng/mL mIL-3. A D4476 dose titration is performed by adding 2.5 µM, 5 µM, 10 µM, 20 µM, and 40 µM D4476 to cell cultures in a final DMSO percentage of 0.4%. Similarly, D4476 is added to LSK cells cultured in SFEM medium supplemented with mTpo and mScf. The number of cells after 96 h of treatment is assessed with CountBright absolute counting beads using flow cytometry[2].
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]. Järås M, et al. Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia. J Exp Med. 2014 Apr 7;211(4):605-12.

Density	1.3±0.1 g/cm3
Boiling Point	675.0±55.0 °C at 760 mmHg
Molecular Formula	C₂₃H₁₈N₄O₃
Molecular Weight	398.414
Flash Point	362.0±31.5 °C
Exact Mass	398.137878
PSA	103.12000
LogP	3.84
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.663
Storage condition	2-8°C

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