Size | Price | Stock | Qty |
---|---|---|---|
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
500mg |
|
||
Other Sizes |
|
Purity: ≥98%
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.
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 |
Molecular Formula |
C23H18N4O3
|
|
---|---|---|
Molecular Weight |
398.41
|
|
CAS # |
301836-43-1
|
|
Related CAS # |
|
|
Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
|
SMILES |
O=C(N)C1=CC=C(C2=NC(C3=CC=C(OCCO4)C4=C3)=C(C5=NC=CC=C5)N2)C=C1
|
|
Synonyms |
|
|
HS Tariff Code |
2934.99.9001
|
|
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 (In Vitro) |
|
|||
---|---|---|---|---|
Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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.
Calculation results
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.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00833417 | Completed Has Results | Drug: Vismodegib 150 mg | Basal Cell Carcinoma | Genentech, Inc. | February 2009 | Phase 2 |