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

規(guī)格	價格	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
更大包裝有超大折扣
400-668-6834 [email protected]

產品質控

批次：純度： 99.43%

99.43

R406相關產品

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

細胞實驗數(shù)據示例

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

生物活性

產品描述

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

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強抑制免疫球蛋白 E (IgE)和 IgG調節(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，K_i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調節(jié)活性，且阻斷B淋巴細胞中BCR調節(jié)活性。^[1] 406 明顯誘導慢性淋巴細胞白血病（CCL）細胞凋亡，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 交叉結合形成的功能。^[4]
實驗圖片	檢測方法	檢測指標	實驗圖片	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

體內研究(In Vivo)
體內研究活性	在已經預防處理的鼠內進行陽性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。^[1] 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。^[3]
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
臨床試驗信息 (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
[1]https://pubmed.ncbi.nlm.nih.gov/16946104/ [2]https://pubmed.ncbi.nlm.nih.gov/19491390/ [3]https://pubmed.ncbi.nlm.nih.gov/21848694/ [4]https://pubmed.ncbi.nlm.nih.gov/17490694/ + 展開

參考文獻

[1]https://pubmed.ncbi.nlm.nih.gov/16946104/
[2]https://pubmed.ncbi.nlm.nih.gov/19491390/
[3]https://pubmed.ncbi.nlm.nih.gov/21848694/

[4]https://pubmed.ncbi.nlm.nih.gov/17490694/

+ 展開

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)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復凍融！	1年-80°C溶于溶劑
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復凍融！	1個月-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

摩爾濃度計算器

體內溶解配方批次：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				動物體內配方計算器
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
澄清溶液	5%DMSO 1 Corn oil 該配方已經過Selleck實驗室實測。如果上述溶解方案不能滿足您的需求，可聯(lián)系Selleck銷售提供定制化測試。	0.500mg/ml (0.80mM)	以 1 mL 工作液為例，取50μL120mg/ml的澄清DMSO儲備液加到950μL玉米油中，混合均勻。工作液請現(xiàn)配現(xiàn)用！
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。

實驗計算

摩爾濃度計算器

質量	濃度	體積	分子量
=	×	×

稀釋計算器分子量計算器

動物體內配方計算器（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）

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

第二步：請輸入動物體內配方組成（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

在訂購、運輸、儲存和使用我們的產品的任何階段，您遇到的任何問題，均可以通過撥打我們的熱線電話400-668-6834，或者技術支持郵箱[email protected]，直接聯(lián)系到我們。我們會在24小時內盡快聯(lián)系您。

操作手冊

如果有其他問題，請給我們留言。

* 必填項

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.

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):

R406

產品質控

R406相關產品

相關信號通路圖

細胞實驗數(shù)據示例

生物活性

化學信息&溶解度

實驗計算

技術支持

常見問題及建議解決方法