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Angiogenesis
Syk inhibitor
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FLT3 inhibitor
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Apoptosis related activator
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FLT inhibitor
R406
僅限科研使用
R406
別名: R406 besylate
R406(R406 besylate) 是一種有效的 Syk 抑制劑，無細胞試驗中IC50為41 nM，對Syk抑制作用強，但是不抑制Lyn，對Flt3的作用比對Syk低5倍。R406 可誘導凋亡。Phase 1。
R406 Chemical Structure
CAS: 841290-81-1
產(chǎn)品質(zhì)控
批次：
純度：
99.43%
99.43
R406相關產(chǎn)品
相關信號通路圖
細胞實驗數(shù)據(jù)示例
| 細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息(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 | ||
| 點擊查看更多細胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | R406(R406 besylate) 是一種有效的 Syk 抑制劑，無細胞試驗中IC50為41 nM，對Syk抑制作用強，但是不抑制Lyn，對Flt3的作用比對Syk低5倍。R406 可誘導凋亡。Phase 1。 | ||||
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| 特性 | Rigel選擇R406作為治療風濕性關節(jié)炎的潛在領先藥物。 | ||||
| 靶點 |
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| 體外研究(In Vitro) | ||||
| 體外研究活性 | R406強抑制免疫球蛋白 E (IgE)和 IgG調(diào)節(jié)的受體信號活性。R406抑制IgE抗體誘導的 LTC4 ，細胞因子和趨化因子的產(chǎn)生和釋放, 包括TNFα, IL-8, 和GM-CSF。R406 抑制肥大細胞中T細胞Syk底物鏈接蛋白的激活和B細胞中B細胞鏈接蛋白/SLP65的磷酸化作用。R406 結合到Syk的ATP結合袋中，抑制Syk的激酶活性， R406是ATP競爭性抑制劑，Ki為30 nM。R406阻斷單核細胞/巨噬細胞和中性白細胞中Syk依賴的FcR調(diào)節(jié)活性，且阻斷B淋巴細胞中BCR調(diào)節(jié)活性。 406 明顯誘導慢性淋巴細胞白血?。–CL）細胞凋亡，且阻斷CCL3和CCL4 分泌。 R406有效抑制血小板信號，且抑制使用特殊抗體或 HIT 病患的血漿通過FcγRIIA 交叉結合形成的功能。 |
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| 實驗圖片 | 檢測方法 | 檢測指標 | 實驗圖片 | PMID |
| Western blot | p-AKT / T-AKT / p-mTOR / T-mTOR p-c-RAF / T-c-RAF p-MEK / T-MEK / p-ERK / T-ERK p-RPS6 / T-RPS6 / p-4E-BP1 / T-4E-BP1 |
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23535559 | |
| Growth inhibition assay | Cell viability (GSC lines) Cell viability (U87, U251 cells) |
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31043589 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | 在已經(jīng)預防處理的鼠內(nèi)進行陽性Arthus 反應，5 mg/kg R406誘導鼠皮膚病變達到86%。R406作用于抗體誘導的關節(jié)炎鼠模型，也有效抑制炎癥。 自身免疫反應時，R406不會影響巨噬細胞和嗜中性粒細胞的功能，免疫毒性為最低水平。 |
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| 動物實驗 | Animal Models | 在C57BL/6鼠中腹腔注射150 μL 取自成年K/BxN鼠的混合血清誘導產(chǎn)生關節(jié)炎。 |
| Dosages | 1 或5 mg/kg | |
| Administration | 口服處理 | |
| 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 |
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化學信息&溶解度
| 分子量 | 628.63 | 分子式 | C22H23FN6O5.C6H6O3S |
| CAS號 | 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 | ||
| 儲存條件(自收到貨起) | |||
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體外溶解度 |
DMSO : 100 mg/mL ( (159.07 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Water : Insoluble Ethanol : 0 mg/mL (0.0 mM) |
摩爾濃度計算器 |
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體內(nèi)溶解配方 現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑 |
動物體內(nèi)配方計算器 | |||||
實驗計算
動物體內(nèi)配方計算器（澄清溶液）
第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）
mg/kg
g
μL
只
第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
計算結果：
工作液濃度： mg/ml；
DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；
體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。
體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。
注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。
技術支持
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常見問題及建議解決方法
問題 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.
