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
CAS: 841290-81-1
产品质控
批次：
纯度：
99.43%
99.43
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 | ||
| 点击查看更多细胞系数据 | |||||
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 |
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| 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] |
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|---|---|---|---|---|
| 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] |
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|---|---|---|
| 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) | |||
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体外溶解度 |
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 |
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体内溶解度 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
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
只
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，注：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：取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：取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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