D4476
Based on 13 publication(s) in Google Scholar
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.
- Purity: 99.89%
- CAS No.: 301836-43-1
- Formula: C23H18N4O3
- Molecular Weight:398.41
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) D4476
More- Nat Commun. 2020 Jan 20;11(1):384. [Abstract]
- Nat Commun. 2021 Sep 10;12(1):5386. [Abstract]
- J Clin Invest. 2025 Oct 28:e191772. [Abstract]
- Stem Cell Res Ther. 2022 May 12;13(1):198. [Abstract]
- Sci Signal. 2026 Jun 23;19(943):eaef1474. [Abstract]
- Commun Biol. 2025 Sep 30;8(1):1384. [Abstract]
- Int J Mol Sci. 2023 Apr 11;24(8):7034. [Abstract]
- Cancers (Basel). 2021 Jul 12;13(14):3477. [Abstract]
- Endocrinology. 2023 Mar 13;164(5):bqad042. [Abstract]
- Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287. [Abstract]
- bioRxiv. 2026 Apr 5.
- bioRxiv. 2024 September 27.
- bioRxiv. 2024 October 01.
Customer Validation & Images
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RT-PCR
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Flow Cytometry
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In Vivo Efficacy Study
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WB
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WB
Biological Activity
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CK1 0.3 μM (IC50) |
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[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 301836-43-1
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Appearance Solid
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Molecular Weight 398.41
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Formula C23H18N4O3
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Color White to yellow
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SMILES
O=C(N)C1=CC=C(C=C1)C(N2)=NC(C3=CC=C4OCCOC4=C3)=C2C5=NC=CC=C5
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Synonyms
Casein Kinase I Inhibitor
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 1 year -20°C 6 months
Publications (13)
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Journal Impact Factor
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Most Recent
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Nat Commun
Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer. [Abstract]2020 Jan 20;11(1):384. PMID: 31959826 -
Nat Commun
Inhibition of CK1ε potentiates the therapeutic efficacy of CDK4/6 inhibitor in breast cancer. [Abstract]2021 Sep 10;12(1):5386. PMID: 34508104
D4476 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2021 Sep 10;12(1):5386. [Abstract]
D4476 (150 mg/kg; i.g.; daily). Combination of D4476 with Ribociclib (100 mg/kg; i.g.; daily) retards MDA-MB-231 tumor growth in vivo.
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J Clin Invest
Molecular glue degrader function of SPOP enhances STING-dependent immunotherapy efficacy in melanoma models. [Abstract]2025 Oct 28:e191772. PMID: 41148213
D4476 purchased from MedChemExpress. Usage Cited in: J Clin Invest. 2025 Oct 28:e191772. [Abstract]
RT-PCR analyses of IFNB1 mRNA in 786-o cells treated first with D4476 (40 μM; 24 h) for 24 h and then with 3 μM diABZI for indicated periods.
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Stem Cell Res Ther
2022 May 12;13(1):198. PMID: 35550648 -
Sci Signal
The APC/C adaptor Cdh1 stabilizes STING to potentiate innate immune activation in renal cell carcinoma. [Abstract]2026 Jun 23;19(943):eaef1474. PMID: 42335217 -
Commun Biol
Casein kinase I isoforms contribute to platelet activation and thrombogenesis via RIPK3-MLKL signaling. [Abstract]2025 Sep 30;8(1):1384. PMID: 41028907
D4476 purchased from MedChemExpress. Usage Cited in: Commun Biol. 2025 Sep 30;8(1):1384. [Abstract]
D4476 (20 µM; 10 min). Flow cytometric analysis of platelet-neutrophil aggregates in whole blood stained with anti-CD62P-PE (specific for platelets), and anti-CD15-APC (specific for neutrophil), followed by addition of TRAP (2 μM) in the presence or absence of CK1 inhibitors, as indicated.
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Int J Mol Sci
Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling. [Abstract]2023 Apr 11;24(8):7034. PMID: 37108197 -
Cancers (Basel)
2021 Jul 12;13(14):3477. PMID: 34298691 -
Endocrinology
2023 Mar 13;164(5):bqad042. PMID: 36929849 -
Biochem Biophys Res Commun
β-catenin stimulates Tcf7l1 degradation through recruitment of casein kinase 2 in mouse embryonic stem cells. [Abstract]2020 Apr 2;524(2):280-287. PMID: 31987502
D4476 purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287. [Abstract]
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 MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2020 Apr 2;524(2):280-287. [Abstract]
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.
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Solvent & Solubility
DMSO : ≥ 50 mg/mL (125.50 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
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
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (277 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
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. [Content Brief]
[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.? [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.5100 mL | 12.5499 mL | 25.0998 mL | 62.7494 mL |
| 5 mM | 0.5020 mL | 2.5100 mL | 5.0200 mL | 12.5499 mL | |
| 10 mM | 0.2510 mL | 1.2550 mL | 2.5100 mL | 6.2749 mL | |
| 15 mM | 0.1673 mL | 0.8367 mL | 1.6733 mL | 4.1833 mL | |
| 20 mM | 0.1255 mL | 0.6275 mL | 1.2550 mL | 3.1375 mL | |
| 25 mM | 0.1004 mL | 0.5020 mL | 1.0040 mL | 2.5100 mL | |
| 30 mM | 0.0837 mL | 0.4183 mL | 0.8367 mL | 2.0916 mL | |
| 40 mM | 0.0627 mL | 0.3137 mL | 0.6275 mL | 1.5687 mL | |
| 50 mM | 0.0502 mL | 0.2510 mL | 0.5020 mL | 1.2550 mL | |
| 60 mM | 0.0418 mL | 0.2092 mL | 0.4183 mL | 1.0458 mL | |
| 80 mM | 0.0314 mL | 0.1569 mL | 0.3137 mL | 0.7844 mL | |
| 100 mM | 0.0251 mL | 0.1255 mL | 0.2510 mL | 0.6275 mL |
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