Lapatinib (GW-572016) Ditosylate

目录号:S1028 别名: GW-572016 中文名称:二苯磺酸拉帕替尼

仅限科研使用

Lapatinib (GW-572016) Ditosylate是一种有效的EGFRErbB2抑制剂,在无细胞试验中IC50分别为10.8和9.2 nM。

Lapatinib (GW-572016) Ditosylate Chemical Structure

CAS: 388082-77-7

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1564.18 现货
RMB 1214.79 现货
RMB 3286.41 现货
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客户使用Selleck生产的Lapatinib (GW-572016) Ditosylate发表文献121篇:

产品安全说明书

HER2抑制剂选择性比较

相关HER2产品

生物活性

产品描述 Lapatinib (GW-572016) Ditosylate是一种有效的EGFRErbB2抑制剂,在无细胞试验中IC50分别为10.8和9.2 nM。
靶点
ErbB2 [1]
(Cell-free assay)
EGFR [1]
(Cell-free assay)
ErbB4 [1]
(Cell-free assay)
9.2 nM 10.8 nM 367 nM
体外研究

Lapatinib 微弱抑制ErbB4活性,IC50为367 nM, 作用于EGFR和 ErbB2 比作用于其他激酶,如c-Src, c-Raf, MEK, ERK, c-Fms, CDK1, CDK2, p38, Tie-2,和 VEGFR-2选择性高300多倍。Lapatinib作用于HN5细胞时,显著抑制受体EGFR 和 ErbB2自磷酸化,这种作用存在剂量依赖性,IC50分别为170 nM和80 nM,而作用于BT474细胞时,IC50分别为210 nM 和 60 nM。与OSI-774和Iressa(ZD1839)优先抑制过量表达EGFR细胞生长不同, Lapatinib 抑制过量表达EGFR和ErbB2细胞生长。 作用于过量表达EGFR或 ErbB2的细胞具有高抑制活性,IC50为0.09-0.21 μM,而作用于表达低水平EGFR或ErbB2的细胞,IC50为3-12 μM,比作用于正常纤维细胞选择性高100倍。Lapatinib有效抑制过量表达EGFR的HN5和A-431细胞生长,也抑制过量表达ErbB2的BT474和N87细胞生长,且显著诱导HN5细胞周期停在G1期,也诱导 BT474 细胞凋亡,与抑制AKT磷酸化相关。[1] Lapatinib 作用于含EGFR的L858R和T790M突变的抗Gefitinib的H1975细胞显著抑制Stat3磷酸化,导致细胞生长受抑制,IC50为1-2 μM。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HN5 cell line MYDQdo9tcW[ncnH0bY9vKGG|c3H5 NVrDNJBqSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIUlUh[2WubDDsbY5mNCCLQ{WwQVAvODJ3IN88US=> MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjR6M{e3Nkc,OTZ2OEO3O|I9N2F-
BT474 cell line M1z4ZnBzd2yrZnXyZZRqd25iYYPzZZk> MoHtRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCEVES3OEBk\WyuIHzpcoUtKEmFNUC9NE4xOjVizszN NVrFXIhyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[0PFM4PzJpPkG2OFg{Pzd{PD;hQi=>
HN5 cell MUfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3u4[GlvcGmkaYTpc44hd2ZiSF61JINmdGxiZ4Lve5RpKGGodHXyJFczKGi{czygTWM2OD1yLkGyJO69VQ>? NHPRW5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNke3O|QyOCd-MU[3O|c1OTB:L3G+
BT474 cell NEXqO2ZIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MoHqTY5pcWKrdHnvckBw\iCEVES3OEBk\WyuIHfyc5d1cCCjZoTldkA4OiCqcoOsJGlEPTB;MD6wPEDPxE1? MlXDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ5N{e0NVAoRjF4N{e3OFExRC:jPh?=
N87 cell MnHIS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NX\SU3J1UW6qaXLpeIlwdiCxZjDOPFch[2WubDDndo94fGhiYX\0[ZIhPzJiaILzMEBKSzVyPUCuNFgh|ryP Mm\rQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ5N{e0NVAoRjF4N{e3OFExRC:jPh?=
HFF cell Mkn5S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NFy3Z|BKdmirYnn0bY9vKG:oIFjGSkBk\WyuIHfyc5d1cCxiSVO1NF06NjlizszN M1Xq[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4N{e3OFExLz5zNke3O|QyODxxYU6=
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MDA-MB-231 MYjBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NVXse4FYSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IHHmeIVzKGi{czDifUBCXFBiY3;ueIVvfCCjc4PhfUwhUUN3ME21MlTPxE1? NInnPXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEG0N|c4QCd-MkCxOFM4Pzh:L3G+
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HepG2 M4nzO2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 MUPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEincFeyJINmdGy|IHHmeIVzKGi{czDifUBCXFBiY3;ueIVvfCCjc4PhfUwhUUN3ME22MlI4|ryP MnHMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjBzNEO3O|goRjJyMUSzO|c5RC:jPh?=
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MIAPaCa NEPDPVVHfW6ldHnvckBie3OjeR?= NX\XSWU2UW6qaXLpeIlwdiCxZjDFVmJjOiCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hVUmDUHHDZUBk\WyuczDifUBGVEmVQTygTWM2OD1yLkG0{txO M3TKN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyOEG3OVI{Lz5{MEixO|UzOzxxYU6=
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CAL27 MVvGeY5kfGmxbjDhd5NigQ>? M2fSXVE3KGi{cx?= MoTFTY5pcWKrdHnvckBw\iCHR1[tbY5lfWOnZDDFS2ZTKHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBESUx{NzDj[YxteyCxdnXy[ZhxemW|c3nu[{BGT0[UIHHmeIVzKDF4IHjyd{BjgSCZZYP0[ZJvKGKub4SsJGlEPTB:MD6wN|LPxE1? M1;3ZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMEiwOlI6Lz5{MUC4NFYzQTxxYU6=
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HeLa Mlm4R5l1d3SxeHnjbZR6KGG|c3H5 NES1UVNEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJ\UyjIHPlcIx{KG:4ZYLlfJBz\XO|aX7nJGhFSUNiYomgdoV{[Xq3cnnuJIR6\SC{ZXT1Z5Rqd25iYYPzZZktKEmFNUC9OU46|ryP M{SyZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMEiwOlI6Lz5{MUC4NFYzQTxxYU6=
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SK-BR-3 NIfaToJCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MljORY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDFdoJDOiCxdnXy[ZhxemW|c3nu[{BpfW2jbjDTT{1DWi1|IHPlcIx{KGK7IF3UWEBie3OjeTygTWM2OD12LkO1{txO NGLuPYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUW3NFg1Oyd-MkG1O|A5PDN:L3G+
MDA-MB-468 NH3PZlRCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NIfydmhCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGVITlJib4\ldoV5eHKnc4PpcochcHWvYX6gUWRCNU2ELUS2PEBk\WyuczDifUBOXFRiYYPzZZktKEmFNUC9NlMvPDcQvF2= NGH5OWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUW3NFg1Oyd-MkG1O|A5PDN:L3G+
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TK10 cell M{XXbmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NUTrN494UW6qaXLpeIlwdiCxZjDoeY1idiCWS{GwJINmdGxiZ4Lve5RpKGmwIHGgZ4VtdCC4aXHibYxqfHliYYPzZZktKEmFNUC9OE4yPjV{MjFOwG0> MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1OVQwLz6VQV7HSXI9N2F-
DSH1 cell MmmwS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? MXTJcohq[mm2aX;uJI9nKGi3bXHuJGRUUDFiY3XscEBoem:5dHigbY4h[SClZXzsJJZq[WKrbHn0fUBie3OjeTygTWM2OD1yLkC5N|k3KM7:TR?= MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1OVQwLz6VQV7HSXI9N2F-
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LB996-RCC cell M1rSSGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NGjMXVBKdmirYnn0bY9vKG:oIHj1cYFvKEyEOUm2MXJESyClZXzsJIdzd3e2aDDpckBiKGOnbHygeoli[mmuaYT5JIF{e2G7LDDJR|UxRTFwM{[yNlgh|ryP NFH2XJk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PTRxJ{7TRW5ITVJ:L3G+
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LS-513 cell MUDHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NV3hdpV4UW6qaXLpeIlwdiCxZjDoeY1idiCOUz21NVMh[2WubDDndo94fGhiaX6gZUBk\WyuII\pZYJqdGm2eTDhd5NigSxiSVO1NF0{NjRyMESxJO69VQ>? MorXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVU1Nyd-U1HOS2VTRC:jPh?=
Assay
Methods Test Index PMID
Western blot p-ErbB2 / t-ErbB2 / p-Akt / t-Akt / p-Erk / t-Erk pEGFR / EGFR / p-mTOR / mTOR / PARP / c-PARP 25238247 28938602
Growth inhibition assay Cell viability 24947784
体内研究 Lapatinib 按~100 mg/kg剂量口服处理,每天两次,显著抑制BT474和HN5移植瘤生长,这种作用存在剂量依赖性。[1] 与在体外活性一致,Lapatinib按100-150 mg/kg剂量处理携带H1975肿瘤的小鼠,延迟肿瘤生长。[3]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
  • 体外激酶实验:

    通过测量抑制肽底物磷酸化的情况而获得抑制酶活性的IC50值。通过杆状病毒表达系统纯化EGFR 和 ErbB2的细胞外激酶域。在96孔圆底板上进行EGFR和ErbB2反应,终体积为45 μL。反应混合物含50 mM 4-吗啉丙磺酸(pH 7.5), 2 mM MnCl2, 10 μM ATP, 1 μCi [γ33P] ATP/每次反应, 50 μM 肽 A [生物素-(氨基)-EEEEYFELVAKKK-CONH2], 1 mM 二流苏糖醇,及 1 μL DMSO(含连续稀释的Lapatinib,起始浓度为10 μM)。加入指定纯化的 1型受体胞内域,开始反应。加入的酶量为为1 pmol/每组反应(20 nM)在23oC下反应10分钟,加入45 μL 0.5%溶于水的磷酸,终止反应。终止反应混合物(75 μL) 转移到磷酸纤维过滤板上。板过滤,然后使用200 μL 0.5% 磷酸冲洗3次。每孔加入闪烁剂(50 μL) , 在Packard Topcount上测量每组反应。通过10点剂量反应曲线获得IC50值。

细胞实验:[1]
  • Cell lines: HFF, MCF-7, T47D, A-431, HN5, BT474, N87, CaLu-3, HB4a, 和 HB4a c5.2
  • Concentrations: 溶于 DMSO,终浓度为~100 μM
  • Incubation Time: 72小时
  • Method: 使用不同浓度Lapatinib处理细胞72小时。使用亚甲基蓝染色测定相对细胞数。使用Spectra酶标仪在620 nm 处测定吸光值。通过碘化丙啶染色和渗透BrdUrd的抗体检测,测量细胞死亡和细胞周期分析。
动物实验:[1]
  • Animal Models: 皮下移植HN5细胞的CD-1雌性裸鼠,皮下移植BT474细胞的 C.B-17 SCID 雌性小鼠
  • Dosages: ~100 mg/kg
  • Administration: 口服处理,每天两次

溶解度(25°C)

体外

体内

从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+40% PEG 300+5% Tween 80+53% ddH2O

1.25 mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 925.46
化学式

C29H26ClFN4O4S.2C7H8O3S

CAS号 388082-77-7
储存条件 3年 -20°C 粉状
2年 -80°C 溶于溶剂

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04608409 Recruiting Drug: Lapatinib and Paclitaxel Ovarian Cancer Frederick R. Ueland M.D.|University of Kentucky November 16 2020 Phase 1
NCT03075995 Unknown status Other: hight-fat breakfast Breast Cancer Sun Yat-sen University April 12 2017 Not Applicable
NCT02338245 Completed Drug: ASLAN001|Drug: Lapatinib|Drug: Capecitabine Metastatic Breast Cancer Aslan Pharmaceuticals December 29 2014 Phase 2
NCT02294786 Terminated Drug: Lapatinib|Drug: Capecitabine|Drug: Octreotide Cancer Novartis Pharmaceuticals|Novartis December 17 2014 Phase 2
NCT02158507 Active not recruiting Drug: Combination of Veliparib + Lapatinib Metastatic Triple Negative Breast Cancer University of Alabama at Birmingham|Breast Cancer Research Foundation of Alabama|GlaxoSmithKline|AbbVie September 2014 Not Applicable
NCT01782651 Completed Drug: Lapatinib plus capecitabine Neoplasms Breast GlaxoSmithKline August 2014 --

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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常见问题及建议解决方法

问题 1:
If I need to use S1028 for treating tumor-bearing mice with injection, how could I prepare the solution?

回答:
S1028 Lapatinib Ditosylate can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as clear solution.

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