R406

別名：R406 besylate

製品コード：S2194 純度：99.43%

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.

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
5mg	JPY 25500	国内在庫あり
10mg	JPY 40500	国内在庫あり
50mg	JPY 130500	国内在庫あり
1g	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] よく尋ねられる質問

文献中Selleckの製品使用例（105）

製品安全説明書

R406関連製品

関連ターゲット	ZAP70	もっと見る
関連製品	R406 (free base) PRT062607 (P505-15) HCl Entospletinib (GS-9973) Fostamatinib (R788) Piceatannol Fostamatinib (R788) disodium BAY-61-3606 PRT-060318 2HCl TAK-659 Fostamatinib disodium hexahydrate RO9021	もっと見る
関連化合物ライブラリー	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	もっと見る

シグナル伝達経路

Syk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 K_i 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
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
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
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

参考
[1] Braselmann S, et al. J Pharmacol Exp Ther, 2006, 319(3), 998-1008. [2] Quiroga MP, et al. Blood, 2009, 114(5), 1029-1037. [3] Lhermusier T, et al. J Thromb Haemost, 2011, 9(10), 2067-2076. [4] Zhu Y, et al. Toxicol Appl Pharmacol, 2007, 221(3), 268-277. + 展開

参考

[4] Zhu Y, et al. Toxicol Appl Pharmacol, 2007, 221(3), 268-277.

+ 展開

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	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

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
=	×	×

希釈計算器分子量計算器

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）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

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

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):