R406

別名:R406 besylate

R406(R406 besylate) is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1.

R406化学構造

CAS No. 841290-81-1

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 42900 国内在庫あり
JPY 25500 国内在庫あり
JPY 40500 国内在庫あり
JPY 130500 国内在庫あり
JPY 598500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール:[email protected]
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文献中Selleckの製品使用例(115)

製品安全説明書

現在のバッチを見る: 純度: 99.43%
99.43

R406関連製品

シグナル伝達経路

Syk阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 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
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生物活性

製品説明 R406(R406 besylate) is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1.
特性 Lead drug candidate for rheumatoid arthritis.
Targets
Flt3 [1]
(Cell-free assay)
Syk [1]
(Cell-free assay)
41 nM
In Vitro
In vitro

R406 is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling. R406 inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with Ki of 30 nM. R406 blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes. [1]

R406 significantly induces chronic lymphocytic leukemia (CLL) cell apoptosis in nurselike cells cocultures and blocks CCL3 and CCL4 secretion by CLL cells in response to B-cell antigen receptor (Bcr) triggering. [2]

R406 is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients. [3]

Kinase Assay In Vitro Fluorescence Polarization Kinase Assay
R406 is serially diluted in DMSO and then diluted to 1% DMSO in kinase buffer (20 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.1 mg/mL acetylated BGG). ATP and substrate in kinase buffer are added at room temperature, resulting in a final DMSO concentration on 0.2%. The kinase reactions are performed in a final volume of 20 mL containing 5mM HS1 peptide substrate, 4 mM ATP and started by addition of 0.125 ng of Syk in kinase buffer. The reaction is allowed to proceed for 40 minutes at room temperature. The reaction is stopped by the addition of 20 mL of PTK quench mix containing EDTA/anti-phosphotyrosine antibody (1X final)/fluorescent phosphopeptide tracer (0.5X final) diluted in FP Dilution Buffer. The plate is incubated for 30 minutes in the dark at room temperature and then read on a Polarion fluorescence polarization plate reader. Data are converted to amount of phosphopeptide present using a calibration curve generated by competition with the phosphopeptide competitor provided in the Tyrosine Kinase Assay Kit. For IC50 determination, R406 is tested at eleven concentrations and curve-fitting is performed by non-linear regression analysis.
実験結果図 Methods Biomarkers 結果図 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
In Vivo
In Vivo

R406 reduces cutaneous reverse passive Arthus reaction by approximately 86% at 5 mg/kg in prophylactic treated mice. R406 also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models. [1]

R406 does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect. [4]

動物実験 動物モデル Arthritis is induced in C57BL/6 mice by intraperitoneal injection of 150 μL of pooled sera from adult K/BxN mice.
投与量 1 or 5 mg/kg
投与経路 Administered orally
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

化学情報

分子量 628.63 化学式

C22H23FN6O5.C6H6O3S

CAS No. 841290-81-1 SDF Download R406 SDFをダウンロードする
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
保管

In vitro
Batch:

DMSO : 100 mg/mL ( (159.07 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : 0 mg/mL

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

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Handling Instructions

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よくある質問(FAQ)

質問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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