R406
For research use only.
Catalog No.S2194
39 publications
CAS No. 841290-81-1
R406 is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1.
Purity & Quality Control
Choose Selective Syk Inhibitors
Biological Activity
| Description | R406 is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | Lead drug candidate for rheumatoid arthritis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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| In vitro |
R406 is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling. R406 inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with Ki of 30 nM. R406 blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes. [1] R406 significantly induces chronic lymphocytic leukemia (CLL) cell apoptosis in nurselike cells cocultures and blocks CCL3 and CCL4 secretion by CLL cells in response to B-cell antigen receptor (Bcr) triggering. [2] R406 is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients. [3] |
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| Cell Data |
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| Assay |
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| In vivo | R406 reduces cutaneous reverse passive Arthus reaction by approximately 86% at 5 mg/kg in prophylactic treated mice. R406 also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models. [1] R406 does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect. [4] |
Protocol
| Animal Research:[1] |
- Collapse
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Solubility (25°C)
| In vitro | DMSO | 100 mg/mL (159.07 mM) |
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| Water | Insoluble | |
| Ethanol | '0 mg/mL | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5%dmso+95%cornoil For best results, use promptly after mixing. |
6mg/mL |
* 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.
Chemical Information
| Molecular Weight | 628.63 |
|---|---|
| Formula | C22H23FN6O5.C6H6O3S |
| CAS No. | 841290-81-1 |
| Storage |
powder in solvent |
| Synonyms | N/A |
| Smiles | CC1(C(=O)NC2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)C.C1=CC=C(C=C1)S(=O)(=O)O |
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 | ||||||||||
| CalculateReset | ||||||||||
Calculation results:
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.
Bio Calculators
Molarity Calculator
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).
Dilution Calculator
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:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Molarity Calculator
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 |
Tech Support
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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Frequently Asked Questions
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Question 1:
What’s the difference between S1533 and S2194?
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Answer:
S1533 and S2194 are two different forms of R406. S1533 is the free base form, containing only R406 molecule without a acid added to it. S2194 has an additional C6H6O3S acid on it which makes the molecule a salt form. The free base and salt forms have same biology activities. Free base has a lower molecular weight and salt form has a better solubility in DMSO.
