1. Cell Cycle/DNA Damage
    Stem Cell/Wnt
    Autophagy
    Apoptosis
  2. Casein Kinase
    Autophagy
    Apoptosis
  3. D4476

D4476 (Synonyms: Casein Kinase I Inhibitor)

Cat. No.: HY-10324 Purity: 99.64%
Handling Instructions

D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC50 value of 0.3 μM in vitro.

For research use only. We do not sell to patients.

D4476 Chemical Structure

D4476 Chemical Structure

CAS No. : 301836-43-1

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10 mM * 1 mL in DMSO USD 99 In-stock
Estimated Time of Arrival: December 31
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10 mg USD 125 In-stock
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50 mg USD 340 In-stock
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Customer Review

Based on 3 publication(s) in Google Scholar

Top Publications Citing Use of Products

    D4476 purchased from MCE. Usage Cited in: Biochem Biophys Res Commun. 2020 Jan 24. pii: S0006-291X(20)30143-1.B

    Western blot analysis of Tcf7l1 protein levels in mESCs pre-treated with the indicative different small molecules for 1 h and then treated with CHIR for 24 h.

    D4476 purchased from MCE. Usage Cited in: Biochem Biophys Res Commun. 2020 Jan 24. pii: S0006-291X(20)30143-1.B

    Western blot analysis of Tcf7l1 protein levels in mESCs pre-treated with D4476 or DMAT and then treated with CHIR or PD03 for 24 h.

    View All Casein Kinase Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    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.

    IC50 & Target[1]

    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].

    Molecular Weight

    398.41

    Formula

    C₂₃H₁₈N₄O₃

    CAS No.

    301836-43-1

    SMILES

    O=C(N)C1=CC=C(C=C1)C(N2)=NC(C3=CC=C4OCCOC4=C3)=C2C5=NC=CC=C5

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 50 mg/mL (125.50 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.27 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (6.27 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (6.27 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [2]

    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].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
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    Keywords:

    D4476Casein Kinase I InhibitorD 4476D-4476Casein KinaseAutophagyApoptosisInhibitorinhibitorinhibit

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