D4476

• CAT Number: I003053
• CAS Number: 301836-43-1
• Molecular Formula: C₂₃H₁₈N₄O₃
• Molecular Weight: 398.41
• Purity: ≥95%
• Target: CK1
• Solubility: DMSO 20 mg/mL
• Storage: 2-8°C
• IC50: 10 uM (IC90 for CK1δ)
• 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)
• InChIKey: DPDZHVCKYBCJHW-UHFFFAOYSA-N
• SMILES: C1COC2=C(O1)C=CC(=C2)C3=C(NC(=N3)C4=CC=C(C=C4)C(=O)N)C5=CC=CC=N5

D4476（Cat No.:I003053） is a highly effective and specific inhibitor of casein kinase 1 (CK1). It demonstrates exceptional cell permeability and inhibits CK1 with an IC50 value of 0.3 μM in vitro. This potent inhibitory activity makes D4476 a valuable tool for studying CK1 signaling pathways and related cellular processes. With its remarkable selectivity and ability to penetrate cells, D4476 serves as a valuable compound for investigating CK1-mediated functions and potential therapeutic applications associated with CK1 dysregulation.

Reference

1:EMBO Rep. 2004 Jan;5(1):60-5. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a.Rena G,Bain J,Elliott M,Cohen P, PMID: 14710188 PMCID: PMC1298959 DOI: 10.1038/sj.embor.7400048 Abstract: The protein kinase CK1 phosphorylates serine residues that are located close to another phosphoserine in the consensus pSer-Xaa-Xaa-Ser. This specificity generates regions in its target proteins containing two or more neighbouring phosphoserine residues, termed here multisite phosphorylation domains (MPDs). In this paper, we demonstrate that 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. Our results indicate that these residues are targeted by CK1 in vivo and that the CK1-mediated phosphorylation of the MPD is required for accelerated nuclear exclusion of FOXO1a in response to IGF-1 and insulin. D4476 is much more potent and specific than IC261 or CKI-7, and is therefore the most useful CK1 inhibitor currently available for identifying physiological substrates of CK1.