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R406 (free base)

现货
Catalog No.
A5880
Syk抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,850.00
现货
5mg
¥ 1,000.00
现货
25mg
¥ 4,000.00
现货
100mg
¥ 10,000.00
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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt470.4
Cas No.841290-80-0
FormulaC22H23FN6O5
Solubility≥23.5mg/mL in DMSO, <2.42 mg/mL in EtOH, <2.56 mg/mL in H2O
Chemical Name6-[[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
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

衍生自人单核细胞或单核细胞系THP-1的人巨噬细胞

溶解方法

在DMSO中的溶解度>11.75mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0-10 μM; 16-20 h; 37°C

应用

在源自人单核细胞或单核细胞系THP-1的人巨噬细胞中,R406有效抑制由FcγR-交联诱导的TNFα产生。大约10倍更高的R406水平抑制LPS诱导的TNFα产生。

动物实验[1]:

动物模型

胶原蛋白抗体诱导的关节炎(CAIA)雌性Balb / c小鼠

剂量

1和5 mg/kg; 口服,每天两次,给药14天

应用

在胶原蛋白抗体诱导的关节炎(CAIA)Balb / c小鼠中,与对照相比,R406在1和5mg / kg下分别将皮肤反向被动Arthus反应减少约72和86%。R406可以抑制由免疫复合物(IC)介导的局部炎性损伤。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

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.

生物活性

Description R406 (free base)是Syk的有效抑制剂,其IC50为41 nM。
靶点 Syk          
IC50 41 nM          

质量控制

质量控制和MSDS

批次:

化学结构

R406(free base)

相关生物数据

R406(free base)

相关生物数据

R406(free base)