Allitinib tosylate

別名: AST-1306 TsOH, AST-6 中文名稱：艾力替尼

目錄號：S2185 Purity: 99.93%

Allitinib (AST-1306, AST-6) 是一種新型，不可逆的EGFR和ErbB2抑制劑，IC50分別為0.5 nM和3 nM，對突變型EGFR T790M/L858R也有效，作用于過表達(dá)ErbB2的細(xì)胞更有效，作用于ErbB家族比作用于其他激酶選擇性高3000倍。

Allitinib tosylate Chemical Structure

CAS: 1050500-29-2

規(guī)格	價格	庫存
10mM (1mL in DMSO)	2990	現(xiàn)貨
5mg	2190.01	現(xiàn)貨
10mg	3021.09	現(xiàn)貨
50mg	8763.3	現(xiàn)貨
200mg	20229.3	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次： S218501 DMSO]124 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false 純度： 99.93%

99.93

Allitinib tosylate相關(guān)產(chǎn)品

相關(guān)靶點(diǎn)	EGFR/ErbB1 HER2/ErbB2 ErbB3 ErbB4 mutant EGFR	點(diǎn)擊展開
相關(guān)產(chǎn)品	AG-490 AG-1478 Canertinib (CI-1033) WZ4002 Rociletinib (CO-1686) Genistein Poziotinib PD153035 HCl PD153035 AEE788 (NVP-AEE788) Pelitinib (EKB-569) Varlitinib Canertinib dihydrochloride Icotinib (BPI-2009H) NSC228155 Nazartinib (EGF816) PD168393 Zorifertinib (AZD3759) Olmutinib (BI 1482694) Daphnetin TAK-285 CL-387785 (EKI-785) AZ5104 Lazertinib Pyrotinib dimaleate WZ8040 Butein CNX-2006 Chrysophanic Acid Norcantharidin Avitinib (Abivertinib) Cyasterone EGFR Inhibitor Alflutinib (Furmonertinib) mesylate WZ3146 Tyrphostin 9 AG-18 EAI045 Naquotinib(ASP8273) Almonertinib (HS-10296) MTX-211 zipalertinib (TAS6417) Tuxobertinib (BDTX-189) (S)-Sunvozertinib ((S)-DZD9008)	點(diǎn)擊展開
相關(guān)化合物庫	激酶抑制劑庫酪氨酸激酶抑制劑分子庫 PI3K/Akt 抑制劑庫細(xì)胞周期化合物庫血管生成相關(guān)化合物庫	點(diǎn)擊展開

細(xì)胞實驗數(shù)據(jù)示例

細(xì)胞系	實驗類型	孵育時間	活性描述	文獻(xiàn)信息(PMID)
NCI-H1975 cells	Proliferation assay	72 h	Antiproliferative activity against human NCI-H1975 cells over-expressing EGFR mutant gene after 72 hrs by SRB assay, IC50=0.7 μM	22227214
A431 cells?	Proliferation assay	72 h	Antiproliferative activity against human A431 cells over-expressing EGFR gene after 72 hrs by SRB assay, IC50=0.2 μM	22227214
A549 cells	Proliferation assay	72 h	Antiproliferative activity against human A549 cells over-expressing EGFR gene after 72 hrs by SRB assay, IC50=6.8 μM	22227214
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
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
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS 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
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH 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

靶點(diǎn)

EGFR ^[1] (Cell-free assay)	ErbB4 ^[1] (Cell-free assay)	ErbB2 ^[1] (Cell-free assay)	EGFR (T790M/L858R) ^[1] (Cell-free assay)
0.5 nM	0.8 nM	3.0 nM	12 nM

體外研究(In Vitro)
體外研究活性	AST-1306選擇性抑制EGFR和ErbB2酪氨酸激酶活性。AST-1306也有效抑制T790M/L858R雙突變型EGFR，IC50為12 nM。AST-1306效果比Lapatinib高500多倍。AST-1306作用于 ErbB 家族激酶比作用于其他激酶家族包括PDGFR, KDR和c-Met選擇性高3000多倍。AST-1306 可能與EGFR和ErbB2氨基酸殘基共價結(jié)合。AST-1306顯著抑制HIH3T3-EGFR T790M/L858R 細(xì)胞生長，存在濃度依賴性。AST-1306作用于HIH3T3-EGFR T790M/L858R 細(xì)胞，有效抑制EGFR磷酸化。而且, AST-1306抑制含EGFR T790M/L858R 突變的NCI-H1975細(xì)胞生長，這種作用存在濃度依賴性。AST-1306抑制EGFR及其下游通路的磷酸化。此外, AST-1306作用于A549細(xì)胞,顯著抑制EGF誘導(dǎo)的EGFR磷酸化，這種作用存在劑量依賴性。AST-1306作用于人癌細(xì)胞包括A549細(xì)胞, Calu-3細(xì)胞和SK-OV-3細(xì)胞，抑制EGFR和ErbB2及其下游信號磷酸化。 ^[1]
激酶實驗	酪氨酸激酶實驗
激酶實驗	在20 μg/mL 聚(Glu,Tyr)4:1預(yù)包被的96孔ELISA 板上測定酪氨酸激酶活性。首先, 每孔中加入在激酶反應(yīng)buffer(50 mM HEPES pH 7.4, 20 mM MgCl₂, 0.1 mM MnCl₂, 0.2 mM Na₃VO₄, 1 mM DTT) 中稀釋的80 μL 5 μM ATP溶液。不同濃度AST-1306 在10 μL 1% DMSO (v/v) 中稀釋，然后加到每孔中，對照組使用1% DMSO (v/v)。隨后，加入在10 μL 激酶反應(yīng)緩沖液中稀釋的純化酪氨酸激酶蛋白，開始激酶反應(yīng)。每種濃度的實驗各進(jìn)行重復(fù)實驗。在37^oC下溫育60分鐘后, 使用含0.1% Tween-20 (T-PBS)的PBS沖洗實驗板三次。然后,加入在含5 mg/mL BSA的T-PBS中稀釋的 100 μL磷酸酪氨酸抗體 (PY99, 按1:500稀釋)。在37^oC下溫育30分鐘后,實驗板再和之前一樣沖洗三次。加入在含5 mg/mL BSA的 T-PBS中按1:2000稀釋的辣根過氧化物酶標(biāo)記的羊抗鼠IgG(100 μL)。然后實驗板在37^oC下預(yù)溫育30分鐘，然后使用 PBS沖洗。最后, 加入100 μL 含0.03 % H₂O₂和溶于0.1 M檸檬酸緩沖液（pH 5.5）的2 mg/mL o-對苯二胺的溶液，與樣本在室溫下溫育，直到出現(xiàn)顏色。加入50 μL 2 M H₂SO₄終止反應(yīng),使用多孔分光光度計在 490 nm處讀數(shù)。測定IC50值。
細(xì)胞實驗	細(xì)胞系	Calu-3和A-549細(xì)胞系
	濃度	0.001-1 μM
	孵育時間	72小時
	方法	使用SRB(Sulforhodamine B)實驗測定細(xì)胞(包括Calu-3, A-549細(xì)胞系等)增殖。細(xì)胞接種在96孔板上，培養(yǎng)24小時。使用濃度不斷增長的AST-1306處理細(xì)胞72小時。維持培養(yǎng)基原樣直到實驗結(jié)束。細(xì)胞與10% 預(yù)冷的三氯乙酸(TCA)在 4^oC下混合1小時，然后在室溫下使用 100 μL溶于1%乙酸的 4 mg/mL SRB 溶液染色15分鐘。移除SRB，然后使用1% 乙酸快速沖洗細(xì)胞5次。晾干細(xì)胞, 蛋白結(jié)合染料在 150 μL 10 mM Tris 堿中溶解5分鐘，然后使用多孔分光光度計在515 nm 測量。測定IC50值。

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	AST-1306每天口服處理SK-OV-3 和Calu-3移植瘤模型，顯著抑制腫瘤生長。AST-1306處理SK-OV-3 模型，7天后，腫瘤幾乎完全消失。相反, AST-1306 作用于HO-8910和A549移植瘤，只稍微抑制腫瘤生長。因此, AST-1306作用于過量表達(dá)ErbB2的腫瘤模型，效果比表達(dá)低水平ErbB2的腫瘤效果高很多。AST-1306耐藥性很好。 Lapatinib作用于過量表達(dá)ErbB2的腫瘤模型，具有抗癌活性，但是按相同劑量及飼喂安排作用于SK-OV-3 移植瘤模型，AST-1306比Lapatinib 效果好。此外, AST-1306 口服處理FVB-2/N^neu模型，每天兩次，持續(xù)3周，顯著抑制腫瘤生長。處理11天后 ,腫瘤幾乎完全消失。在藥物處理期間，鼠體重降低小于20% 。^[1]
動物實驗	Animal Models	攜帶SK-OV-3移植瘤的裸鼠和SK-OV-3FVB-2/N^neu轉(zhuǎn)基因鼠
	Dosages	25 mg/kg, 50 mg/kg和100 mg/kg
	Administration	口服處理,每天兩次

參考文獻(xiàn)
https://pubmed.ncbi.nlm.nih.gov/21789172/

參考文獻(xiàn)

https://pubmed.ncbi.nlm.nih.gov/21789172/

化學(xué)信息&溶解度

分子量	621.08	分子式	C₂₄H₁₈ClFN₄O₂,C₇H₈O₃S
CAS號	1050500-29-2	SDF	Download Allitinib tosylate SDF
Smiles	CC1=CC=C(C=C1)S(=O)(=O)O.C=CC(=O)NC1=CC2=C(C=C1)N=CN=C2NC3=CC(=C(C=C3)OCC4=CC(=CC=C4)F)Cl
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(fù)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(fù)凍融！	1個月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 124 mg/mL ( (199.65 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計算器

體內(nèi)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(nèi)配方計算器

實驗計算

摩爾濃度計算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計算器分子量計算器

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）

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(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(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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