R406

别名: R406 besylate

R406(R406 besylate) 是一种有效的 Syk 抑制剂,无细胞试验中IC50为41 nM,对Syk抑制作用强,但是不抑制Lyn,对Flt3的作用比对Syk低5倍。R406 可诱导凋亡。Phase 1。

R406 Chemical Structure

R406 Chemical Structure

CAS: 841290-81-1

规格 价格 库存 购买数量
10mM (1mL in DMSO) 2341.19 现货
5mg 1421.87 现货
50mg 7119.85 现货
1g 32678.1 现货
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R406相关产品

相关信号通路图

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
LY3 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
LY7 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
DHL4 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
Raji  Apoptosis Assay 0/3/10 μM 48 h induces cell death significantly 20875408
Jeko-1  Apoptosis Assay 0/3/10 μM 48 h induces cell death significantly 20875408
DoHH2 Apoptosis Assay 0/3/10 μM 48 h induces cell death significantly 20875408
platelet  Function Assay 0.05/1/2.5 μM 5 min inhibits the signaling mechanisms downstream of FcγRIIA 21848694
platelet  Function Assay 1 μm 5 min inhibits FcγRIIA-mediated platelet aggregation 21848694
RL Function Assay 1/2.5 μM 24 h reduces the activation of Akt and p70S6K 21926965
RL Function Assay 2.5/5 μM 24/48 h induces a potent decrease in MMP-9 mRNA expression 21926965
JB7 Growth Inhibition Assay 0-2.5 μM 48 h induces cell cycle arrest 23398911
AB5 Growth Inhibition Assay 0-2.5 μM 48 h induces cell cycle arrest 23398911
JB7 Apoptosis Assay 0-2.5 μM 48 h induces apoptosis 23398911
AB5 Apoptosis Assay 0-2.5 μM 48 h induces apoptosis 23398911
HMECs Function Assay 0-10 μM 20 min inhibits VEGF-stimulated release of NO 24329544
CFSE-CD11b+ Growth Inhibition Assay 0.0625-1 μM 8 d blocks proliferation of GVHD-derived CD4+ T cells and CD11b+ cells 24679982
CFSE-CD4+ T  Growth Inhibition Assay 0.0625-1 μM 4 d blocks proliferation of GVHD-derived CD4+ T cells and CD11b+ cells 24679982
PBMCs Function Assay 5 μM 1 h decreases the cell migration 25127862
PBMCs Cell Viability Assay 0-50 μM 24 h inhibits cell viability dose dependently 25127862
primary MCL Apoptosis Assay 2 µM 24 h increases significantly apoptosis  25388373
Jeko-1 Apoptosis Assay 5 μM 24 h induces 25.1 ± 3.2 % apoptosis 25835755
U266 Function Assay 1 μM 3 h reduces migration  26251761
AMO-1 Function Assay 1 μM 3 h reduces migration  26251761
DHL6 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
LY10 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
DHL10 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
Wsu-NHL Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
LY18 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
LY1 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
DHL8 Apoptosis Assay 0/1/4 μM 96 h induces apoptosis dose dependently 18006696
DHL4 Apoptosis Assay 4 μM 96 h induces cleavage of caspases 9 and 3, but not caspase 8 18006696
DHL6 Apoptosis Assay 4 μM 96 h induces cleavage of caspases 9 and 3, but not caspase 8 18006696
LY3 Apoptosis Assay 4 μM 96 h induces cleavage of caspases 9 and 3, but not caspase 8 18006696
LY7 Apoptosis Assay 4 μM 96 h induces cleavage of caspases 9 and 3, but not caspase 8 18006696
DHL4 Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
LY7 Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
LY3 Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
DHL6 Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
LY10 Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
Wsu-NHL Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
LY18 Function Assay 4 μM 16 h inhibits tonic BLNK tyrosine phosphorylation 18006696
Rec1 Function assay 2.5 uM 6 hrs Inhibition of BTK phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method 25222877
Rec1 Function assay 2.5 uM 6 hrs Inhibition of Syk phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method 25222877
Rec1 Function assay 2.5 uM 6 hrs Inhibition of Lyn phosphorylation in human Rec1 cells at 2.5 uM incubated for 6 hrs by Western blotting method 25222877
Mino Growth Inhibition Assay 48 h IC50=5.70854 μM 25835755
Jeko-1 Growth Inhibition Assay 48 h IC50=5.06826 μM 25835755
MV411 Function assay 72 hrs Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry, EC50=0.01μM. 24779514
TF1 Function assay 1 hr Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation, EC50=0.013μM. 24779514
SK-M-MC Function assay 1 hr Inhibition of Ret in human SK-M-MC cells assessed as assessed as phosphorylation after 1 hr incubation, EC50=0.036μM. 24779514
mast cells Function assay 1 hr Inhibition of cKit in stem cell factor-stimulated bone marrow derived mouse mast cells assessed as phosphorylation after 1 hr incubation, EC50=0.046μM. 24779514
B-cells Function assay 1 hr Inhibition of Syk in alphaIgM-stimulated human B cells assessed as cell proliferation after 1 hr incubation by flow cytometry, EC50=0.151μM. 24779514
B-cells Function assay 1 hr Inhibition of Syk in alphaIgM-stimulated human B cells assessed as CD86 expression after 1 hr incubation by flow cytometry, EC50=0.335μM. 24779514
neutrophils Function assay Inhibition of SYK in human neutrophils cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.033μM. 22257213
B-cells Function assay Inhibition of SYK in human B-cells cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.048μM. 22257213
Ramos Function assay Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay, EC50=0.053μM. 24779514
mesangial cells Function assay Inhibition of SYK in cultured human mesangial cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.056μM. 22257213
SK-N-SH Function assay Inhibition of Ret in human SK-N-SH cells, EC50=0.08μM. 22257213
mouse bone marrow cells Function assay Inhibition of IL3 dependent proliferation in C57/B16 mouse bone marrow cells using [3H]thymidine by liquid scintillation counting, IC50=0.147μM. 24726806
THP1 Function assay Inhibition of SYK in human THP1 cells assessed as reduction in FcepsilonR1/FcgammaR-mediated signaling responses, EC50=0.171μM. 22257213
Ramos Function assay Inhibition of Syk in anti IgM-stimulated human Ramos cells assessed as BLNK phosphorylation by cellular assay, IC50=0.457μM. 24726806
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
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生物活性

产品描述 R406(R406 besylate) 是一种有效的 Syk 抑制剂,无细胞试验中IC50为41 nM,对Syk抑制作用强,但是不抑制Lyn,对Flt3的作用比对Syk低5倍。R406 可诱导凋亡。Phase 1。
特性 Rigel选择R406作为治疗风湿性关节炎的潜在领先药物。
靶点
Flt3 [1]
(Cell-free assay)
Syk [1]
(Cell-free assay)
41 nM
体外研究(In Vitro)
体外研究活性

R406强抑制免疫球蛋白 E (IgE)和 IgG调节的受体信号活性。R406抑制IgE抗体诱导的 LTC4 ,细胞因子和趋化因子的产生和释放, 包括TNFα, IL-8, 和GM-CSF。R406 抑制肥大细胞中T细胞Syk底物链接蛋白的激活和B细胞中B细胞链接蛋白/SLP65的磷酸化作用。R406 结合到Syk的ATP结合袋中,抑制Syk的激酶活性, R406是ATP竞争性抑制剂,Ki为30 nM。R406阻断单核细胞/巨噬细胞和中性白细胞中Syk依赖的FcR调节活性,且阻断B淋巴细胞中BCR调节活性。[1]

406 明显诱导慢性淋巴细胞白血病(CCL)细胞凋亡,且阻断CCL3和CCL4 分泌。[2]

R406有效抑制血小板信号,且抑制使用特殊抗体或 HIT 病患的血浆通过FcγRIIA 交叉结合形成的功能。[4]

实验图片 检测方法 检测指标 实验图片 PMID
Western blot p-RPS6 / T-RPS6 / p-4E-BP1 / T-4E-BP1 p-MEK / T-MEK / p-ERK / T-ERK p-c-RAF / T-c-RAF p-AKT / T-AKT / p-mTOR / T-mTOR 23535559
Growth inhibition assay Cell viability (U87, U251 cells) Cell viability (GSC lines) 31043589
体内研究(In Vivo)
体内研究活性

在已经预防处理的鼠内进行阳性Arthus 反应,5 mg/kg R406诱导鼠皮肤病变达到86%。R406作用于抗体诱导的关节炎鼠模型,也有效抑制炎症。[1]

自身免疫反应时,R406不会影响巨噬细胞和嗜中性粒细胞的功能,免疫毒性为最低水平。[3]

动物实验 Animal Models 在C57BL/6鼠中腹腔注射150 μL 取自成年K/BxN鼠的混合血清诱导产生关节炎。
Dosages 1 或5 mg/kg
Administration 口服处理
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01725230 Completed
Rheumatoid Arthritis
AstraZeneca
November 2012 Phase 1
NCT01598571 Completed
Healthy
AstraZeneca
May 2012 Phase 1
NCT01387308 Completed
Healthy
AstraZeneca
August 2011 Phase 1
NCT01355354 Completed
Healthy Volunteers|Rheumatoid Arthritis
AstraZeneca
June 2011 Phase 1

化学信息&溶解度

分子量 628.63 分子式

C22H23FN6O5.C6H6O3S

CAS号 841290-81-1 SDF Download R406 SDF
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
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 100 mg/mL ( (159.07 mM) ;DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Water : Insoluble

Ethanol : 0 mg/mL (0.0 mM)

摩尔浓度计算器

体内溶解度
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

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常见问题及建议解决方法

问题 1:
What’s the difference between S1533 and S2194?

回答:
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.

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