- 抑制剂
- 化合物库
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- 生物试剂
- qPCR
- 2x SYBR Green qPCR Master Mix
- 2x SYBR Green qPCR Master Mix(Low ROX)
- 2x SYBR Green qPCR Master Mix(High ROX)
- 蛋白实验
- Protein A/G免疫沉淀磁珠
- Anti-DYKDDDDK Tag免疫磁珠
- Anti-DYKDDDDK Tag亲和凝胶
- Anti-Myc免疫磁珠
- Anti-HA免疫磁珠
- 磁力架
- Poly DYKDDDDK Tag多肽
- 细胞核与细胞浆蛋白抽提试剂盒
- 免疫磁珠
- 蛋白酶抑制剂Cocktail
- 蛋白酶抑制剂Cocktail(DMSO储液)
- 磷酸酶抑制剂Cocktail
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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(PMID) |
|---|---|---|---|---|---|
| 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] |
|
|---|---|---|
| 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 |
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 |
|
体内溶解配方 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 this compound. S1533 is the free base form, containing only its molecule without an 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.
