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R406

现货
Catalog No.
A8546
SYK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,400.00
现货
2mg
¥ 800.00
现货
5mg
¥ 1,000.00
现货
25mg
¥ 2,800.00
现货

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Background

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.

文献引用

1. Gao D, Wang L, et al. "Spleen tyrosine kinase SYK(L) interacts with YY1 and coordinately suppresses SNAI2 transcription in lung cancer cells." FEBS J. 2018 Sep 24. PMID:30251328

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt628.63
Cas No.841290-81-1
FormulaC22H23FN6O5.C6H6O3S
Solubility≥31.45mg/mL in DMSO
Chemical Namebenzenesulfonic acid;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
SDFDownload SDF
Canonical SMILESCC1(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
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

人类肥大细胞

制备方法

该化合物在DMSO中的溶解度大于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

EC50:56 nM,30 min

实验结果

将细胞与R406或DMSO孵育30分钟,然后用0.25至2 mg/ml抗IgE或抗IgG或2 μM离子霉素刺激,R406以剂量依赖性方式抑制抗IgE介导的CHMC脱颗粒,测定为类胰蛋白酶释放,但对离子霉素触发的类胰蛋白酶释放没有活性,表明R406对FcR信号传导而不是脱颗粒本身具有特异性,这种特异性抑制也意味着R406作用位点靠近受体复合物和钙动员的上游。

动物实验: [1]

动物模型

雌性C57BL/6小鼠

给药剂量

口服给药,0.1、0.5、1和5 mg/kg

实验结果

在免疫复合物介导的小鼠炎症模型中,研究R406抑制反向被动Arthus反应的能力。与对照相比,在免疫复合物攻击前1小时,使用R406对小鼠进行处理,在1和5 mg/kg下分别使皮肤反向被动Arthus反应减少约72和86%。1和5 mg/kg R406处理后提取的外渗染料的净光密度读数从对照组的0.14分别降低至0.04或0.02。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] 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. Journal of Pharmacology and Experimental Therapeutics, 2006, 319(3): 998-1008.

生物活性

Description R406是高效的Syk抑制剂,其IC50值为41 nM。
靶点 Syk          
IC50 41 nM          

质量控制

化学结构

R406

相关生物数据

R406

相关生物数据

R406

相关生物数据

R406