R406

別名: R406 besylate

目錄號：S2194 Purity: 99.43%

R406(R406 besylate) 是一種有效的 Syk 抑制劑，無細(xì)胞試驗(yàn)中IC50為41 nM，對Syk抑制作用強(qiáng)，但是不抑制Lyn，對Flt3的作用比對Syk低5倍。R406 可誘導(dǎo)凋亡。Phase 1。

R406 Chemical Structure

CAS: 841290-81-1

規(guī)格	價(jià)格	庫存
10mM (1mL in DMSO)	2341.19	現(xiàn)貨
5mg	1421.87	現(xiàn)貨
50mg	7119.85	現(xiàn)貨
1g	32678.1	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.43%

99.43

R406相關(guān)產(chǎn)品

相關(guān)靶點(diǎn)	ZAP70	點(diǎn)擊展開
相關(guān)產(chǎn)品	R406 (free base) PRT062607 (P505-15) HCl Entospletinib (GS-9973) Piceatannol BAY-61-3606 PRT-060318 2HCl TAK-659 Hydrochloride RO9021	點(diǎn)擊展開
相關(guān)化合物庫	酪氨酸激酶抑制劑分子庫 PI3K/Akt 抑制劑庫血管生成相關(guān)化合物庫 HIF-1信號通路化合物庫 FDA抗癌藥物庫	點(diǎn)擊展開

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	給藥濃度	孵育時(shí)間	活性描述	文獻(xiàn)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
點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù)

生物活性

產(chǎn)品描述

特性

Rigel選擇R406作為治療風(fēng)濕性關(guān)節(jié)炎的潛在領(lǐng)先藥物。

靶點(diǎn)

Flt3 ^[1] (Cell-free assay)	Syk ^[1] (Cell-free assay)
	41 nM

體外研究(In Vitro)
體外研究活性	R406強(qiáng)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(dǎo)的 LTC4 ，細(xì)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(xì)胞中T細(xì)胞Syk底物鏈接蛋白的激活和B細(xì)胞中B細(xì)胞鏈接蛋白/SLP65的磷酸化作用。R406 結(jié)合到Syk的ATP結(jié)合袋中，抑制Syk的激酶活性， R406是ATP競爭性抑制劑，K_i為30 nM。R406阻斷單核細(xì)胞/巨噬細(xì)胞和中性白細(xì)胞中Syk依賴的FcR調(diào)節(jié)活性，且阻斷B淋巴細(xì)胞中BCR調(diào)節(jié)活性。^[1] 406 明顯誘導(dǎo)慢性淋巴細(xì)胞白血?。–CL）細(xì)胞凋亡，且阻斷CCL3和CCL4 分泌。^[2] 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(jié)合形成的功能。^[4]
實(shí)驗(yàn)圖片	檢測方法	檢測指標(biāo)	實(shí)驗(yàn)圖片	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

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	在已經(jīng)預(yù)防處理的鼠內(nèi)進(jìn)行陽性Arthus 反應(yīng)，5 mg/kg R406誘導(dǎo)鼠皮膚病變達(dá)到86%。R406作用于抗體誘導(dǎo)的關(guān)節(jié)炎鼠模型，也有效抑制炎癥。^[1] 自身免疫反應(yīng)時(shí)，R406不會(huì)影響巨噬細(xì)胞和嗜中性粒細(xì)胞的功能，免疫毒性為最低水平。^[3]
動(dòng)物實(shí)驗(yàn)	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(dǎo)產(chǎn)生關(guān)節(jié)炎。
	Dosages	1 或5 mg/kg
	Administration	口服處理

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

參考文獻(xiàn)
[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

參考文獻(xiàn)

[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

化學(xué)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(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1個(gè)月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 100 mg/mL ( (159.07 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請使用新開封DMSO)

Water : Insoluble

Ethanol : 0 mg/mL (0.0 mM)

DMSO : 126 mg/mL ( (200.43 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請使用新開封DMSO)

Ethanol : 8 mg/mL (12.72 mM)

Water : Insoluble

DMSO : 100 mg/mL ( (159.07 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請使用新開封DMSO)

Ethanol : 38 mg/mL (60.44 mM)

Water : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

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(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計(jì)算器分子量計(jì)算器

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過程中的損耗，建議多配一只動(dòng)物的藥量）

給藥劑量 mg/kg 動(dòng)物平均體重 g 每只動(dòng)物給藥體積 μL 動(dòng)物數(shù)量只

第二步：請輸入動(dòng)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(jì)算結(jié)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(jìn)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。

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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 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):

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R406

產(chǎn)品質(zhì)控

R406相關(guān)產(chǎn)品

相關(guān)信號通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

生物活性

化學(xué)信息&溶解度

實(shí)驗(yàn)計(jì)算

技術(shù)支持

常見問題及建議解決方法