R406 (free base)
For research use only.
Molecular Weight(MW): 470.45
R406 (free base) is a potent Syk inhibitor with IC50 of 41 nM in a cell-free assay, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 (free base) triggers apoptosis. Phase 1.
Selleck's R406 (free base) has been cited by 58 publications
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|Description||R406 (free base) is a potent Syk inhibitor with IC50 of 41 nM in a cell-free assay, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 (free base) triggers apoptosis. Phase 1.|
R406 is an ATP-competitive inhibitor of Syk with a Ki value of 30 nM. R406 selectively inhibits Syk-dependent signaling with EC50 values ranging from 33 nM to 171 nM, more potently than Syk-independent pathways in different cells.  R406 inhibits cellular proliferation of a large panel of diffuse large B-cell lymphoma (DLBCL) cell lines at EC50 values ranging from 0.8 μM to 8.1 μM. R406 treatment (1 μM or 4 μM) induces the activation of caspases 9 and 3, but not caspase 8, leading to significant apoptosis of the majority of DLBCL cell lines. Pretreatment of R406 completely blocks the phosphorylation of SYK525/526 and the SYK-dependent phosphorylation of BLNK in R406-sensitive DLBCLs following B-cell receptor (BCR) crosslinking.  R406 potently decreases MMP-9 mRNA levels by 2.8- and 4.3-fold lower than controls after 24 and 48 hours treatment, respectively, and reduces the invasive capacity of the RL cells. 
|In vivo||R406 has shown efficacy in a number of animal models of immune disorders. Oral administration of R406 in mice with immune complex-mediated inflammation significantly inhibits the cutaneous reverse passive Arthus reaction by approximately 72% and 86% at 1 mg/kg and 5 mg/kg, respectively, compared with the control. R406 treatment at 10 mg/kg significantly reduces inflammation and swelling, decreases the progressive arthritis to a lower level in the passive anticollagen antibody-challenged mice, and delays the onset and reduces paw thickening and clinical arthritis by approximately 50% in the K/BxN serum transfer mice model. |
In-vitro Fluorescence Polarization Kinase Assays:R406 is serially diluted in DMSO and then diluted to 1% DMSO in kinase buffer (20 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.1 mg/mL acetylated BGG). ATP and substrate in kinase buffer are added at room temperature, resulting in a final DMSO concentration on 0.2%. The kinase reactions are performed in a final volume of 20 μL containing 5 μM HS1 peptide substrate and 4 μM ATP and started by addition of 0.125 ng of Syk in kinase buffer. The reaction is allowed to proceed for 40 minutes at room temperature. The reaction is stopped by the addition of 20 μL of PTK quench mix containing EDTA/anti-phosphotyrosine antibody (1X final)/fluorescent phosphopeptide tracer (0.5X final) diluted in FP Dilution Buffer. The plate is incubated for 30 minutes in the dark at room temperature and then read on a Polarion fluorescence polarization plate reader. Data are converted to amount of phosphopeptide present using a calibration curve generated by competition with the phosphopeptide competitor provided in the Tyrosine Kinase Assay Kit. For IC50 determination, R406 is tested at eleven concentrations in duplicate and curve-fitting is performed by non-linear regression analysis using Prism GraphPad Software.
|In vitro||DMSO||21 mg/mL (44.63 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
1% DMSO+30% polyethylene glycol+1% Tween 80
For best results, use promptly after mixing.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
In vivo Formulation Calculator (Clear solution)
|Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)|
|Dosage||mg/kg||Average weight of animals||g||Dosing volume per animal||ul||Number of animals|
|Step 2: Enter the in vivo formulation ()|
|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
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Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01725230||Completed||Drug: Fostamatinib|Drug: Rosuvastatin|Drug: Simvastatin||Rheumatoid Arthritis||AstraZeneca||November 2012||Phase 1|
|NCT01598571||Completed||Drug: Fostamatinib||Healthy||AstraZeneca||May 2012||Phase 1|
|NCT01387308||Completed||Drug: Fostamatinib||Healthy||AstraZeneca||August 2011||Phase 1|
|NCT01355354||Completed||Drug: Digoxin|Drug: Fostamatinib||Healthy Volunteers|Rheumatoid Arthritis||AstraZeneca||June 2011||Phase 1|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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