D 4476

Alias: D-4476; D4476; Casein Kinase I Inhibitor; D 4476
Cat No.:V0958 Purity: ≥98%
D 4476 (D-4476; D4476; Casein Kinase I Inhibitor) is a potent, selective, and cell-permeantinhibitor of CK1 (casein kinase 1) with potential antitumor activity.
D 4476 Chemical Structure CAS No.: 301836-43-1
Product category: Casein Kinase
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

D 4476 (D-4476; D4476; Casein Kinase I Inhibitor) is a potent, selective, and cell-permeant inhibitor of CK1 (casein kinase 1) with potential antitumor activity. It inhibits CK1 from Schizosaccharomyces pombe and CK1δ with IC50s of 200 nM and 300 nM in a cell-free assay, respectively. It also acts as an ALK5 inhibitor with IC50 of 500 nM. D4476 suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. 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.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
D4476 is an intracellular and in vitro strong and highly selective CK1 inhibitor. D4476 selectively prevents endogenous forkhead box transcription factor O1a (FOXO1a) from becoming phosphorylated on Ser322 and Ser325 within its MPD in H4IIE liver cancer cells, while leaving other sites unaffected. With 0.1 mM ATP and the phosphorylated peptide TFRPRTSpSNASTIS, which corresponds to FOXO1a residues 312–325, CK1δ was suppressed with an IC50 value of 0.3 μM. D4476 is an ATP competitive inhibitor of CK1, as seen by the progressive fall in the IC50 value of CK1δ when the ATP concentration drops [1].
ln Vivo

Animal Protocol


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
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C23H18N4O3
Molecular Weight
398.41
CAS #
301836-43-1
SMILES
O=C(N)C1=CC=C(C2=NC(C3=CC=C(OCCO4)C4=C3)=C(C5=NC=CC=C5)N2)C=C1
Synonyms
D-4476; D4476; Casein Kinase I Inhibitor; D 4476
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 79 mg/mL (198.3 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.5100 mL 12.5499 mL 25.0998 mL
5 mM 0.5020 mL 2.5100 mL 5.0200 mL
10 mM 0.2510 mL 1.2550 mL 2.5100 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

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Biological Data
  • D 4476

    D4476 specifically inhibits the phosphorylation at Ser322 and Ser325 specifically in H4IIE cells. EMBO Rep. 2004 Jan;5(1):60-5.
  • D 4476

    D4476 inhibits IGF-1 and serum-stimulated nuclear exclusion of FOXO1a in living cells. EMBO Rep. 2004 Jan;5(1):60-5.
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