R406(free base) |
| Catalog No.GC15658 |
R406(유리 염기)은 30nM의 Ki로 ATP 결합에 대해 경구로 이용 가능하고 경쟁적인 Syk/FLT3 억제제이며, Km 값에 해당하는 ATP 농도에서 측정된 41nM의 IC50으로 시험관 내에서 Syk 키나제 활성을 강력하게 억제합니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 841290-80-0
Sample solution is provided at 25 µL, 10mM.
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R406 is a potent SYK inhibitorSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase mainly expressed in hematopoietic cells. It transmits signals from a variety of cell surface receptors including CD74, Fc receptor and integrins. It is crucial for adaptive immune response, and also very important for cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development. [1]
Functional abnormality of SYK has been implicated in several blood malignancies. Constitutively active SYK can transform B cells. SYK inhibition can be beneficial for patients with blood cancers and autoimmune diseases.
R406 is a potent inhibitor of IgE and IgG mediated Fc receptor activation with EC50 for degranulation of 56-64 nM. [2] R406 targets SYK and inhibits phosphorylation of SYK substrates by binding to its ATP binding pocket and competing with ATP. R406 strongly inhibits SYK kinase activity with an IC50 of 41 nM.
R406 induces apoptosis in diffuse large B-cell lymphoma cell lines. It blocks B cell receptor signaling through inhibiton of SYK autophosphorylation of Y525/Y526 and SYK-dependent phosphorylation of the B-cell linker protein. [3]
R406 can be administrated orally.
References:
[1]Mocsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol 2010. 10(6): 387-402.
[2]Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 2006. 319(3): 998-1008.
[3]Chen L, Monti S, Juszczynski P, et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 2008. 111(4): 2230*2237.
| Cell experiment [1]: | |
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Cell lines |
human macrophages derived from human monocytes or the monocytic cell line THP-1 |
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Preparation method |
The solubility of this compound in DMSO is >11.75mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0-10 μM; 16 to 20 h; 37°C |
|
Applications |
In human macrophages derived from human monocytes or the monocytic cell line THP-1, R406 potently inhibited TNFα production induced by FcγR-cross-linking. Roughly 10-fold higher levels of R406 inhibited TNFα production induced by LPS. |
| Animal experiment [1]: | |
|
Animal models |
collagen antibody-induced arthritis (CAIA) female Balb/c mice |
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Dosage form |
1 and 5 mg/kg; orally b.i.d for 14 days |
|
Application |
In collagen antibody-induced arthritis (CAIA) Balb/c mice, R406 reduced the cutaneous reverse passive Arthus reaction by approximately 72 and 86% at 1 and 5 mg/kg, respectively, compared with the vehicle control. R406 could inhibit local inflammatory injury mediated by immune complexs (ICs). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Braselmann S1, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008. | |
| Cas No. | 841290-80-0 | SDF | |
| Chemical Name | 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one | ||
| Canonical SMILES | CC1(C(=O)NC2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)C | ||
| Formula | C22H23FN6O5 | M.Wt | 470.4 |
| Solubility | ≥ 23.5mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1259 mL | 10.6293 mL | 21.2585 mL |
| 5 mM | 0.4252 mL | 2.1259 mL | 4.2517 mL |
| 10 mM | 0.2126 mL | 1.0629 mL | 2.1259 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)
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