产品说明书

Lapatinib

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Chemical Structure| 231277-92-2 同义名 : GW572016;GW2016;GSK572016
CAS号 : 231277-92-2
货号 : A254504
分子式 : C29H26ClFN4O4S
纯度 : 98%
分子量 : 581.058
MDL号 : MFCD09264194
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(206.52 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+35% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 45 mg/mL suspension

生物活性
靶点

  • EGFR/ErbB1

    EGFR, IC50:10.8 nM

  • HER2/ErbB2

    ErbB2, IC50:9.2 nM

  • ErbB4

    ErbB4, IC50:367 nM

  • HER2

    ErbB2, IC50:9.2 nM
描述 EGFR (epidermal growth factor receptor) family consists of four members that belong to the ErbB lineage of proteins (ErbB1 - 4) with an external domain that binds activating ligands, such as EGF, and is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. Upon activation, EGFR phosphorylates both the receptor itself and a variety of “effector” protein. Lapatinib is a dual inhibitor of both EGFR and ErbB2 with IC50 values of 10.8 nM and 9.2 nM (measured by kinase activity), respectively, 300-fold selective over other kinases tested except for ErbB-4 (IC50 = 367 nM). Treatment with Lapatinib for 6h inhibited receptor autophosphorylation of EGFR and ErbB-2, as well as phosphorylation of serine-473 of AKT, the key signal transduction mediator, in a dose-responsive manner at concentration ranged from 0.03 to 10 μM in BT474 and HN5 cell lines. Lapatinib showed growth inhibition with IC50 values ranged from 0.09 - 12μM in EGFR-overexpressing cell lines HN5 and A-431, the ErbB-2-overexpressing cell lines BT474, N87 and CaLu-3,as well as tumor cell lines expressing low levels of EGFR and ErbB-2, MCF-7 and T47D cells. Treatment with 1 and 10 μM Lapatinib resulted in induction of G1 arrest and increased number of cells with sub-2N DNA content, consistent with cell death by an apoptotic mechanism, in EGFR-overexpressing cell line, HN5, and BT474 cells. Complete inhibition of tumor growth was seen at dose of 100mg/kg, orally, twice daily, in BT474 and HN5 human tumor xenografts[1].
作用机制 Lapatinib binds reversibly and a very slow off-rate to the ATP binding pocket in an inactive-like conformation, thus preventing autophosphorylation of the target[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A101D Growth Inhibition Assay IC50=20.8587 μM SANGER
A253 Growth Inhibition Assay IC50=1.97335 μM SANGER
A388 Growth Inhibition Assay IC50=0.72258 μM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00555152 Ductal Breast Carcinoma In Sit... 展开 >>u HER2/Neu Positive 收起 << Not Applicable Completed - United States, Alabama ... 展开 >> University of Alabama at Birmingham Cancer Center Birmingham, Alabama, United States, 35233 United States, Texas M D Anderson Cancer Center Houston, Texas, United States, 77030 收起 <<
NCT00555152 - Completed - -
NCT00999804 Breast Cancer Phase 2 Active, not recruiting January 2018 United States, Alabama ... 展开 >> University of Alabama - Birmingham Birmingham, Alabama, United States, 35294 United States, Illinois University of Chicago Chicago, Illinois, United States, 60637 United States, Indiana Indiana University Indianapolis, Indiana, United States, 46202 United States, Maryland Johns Hopkins Baltimore, Maryland, United States, 21231 United States, Massachusetts Dana Farber Cancer Institute Boston, Massachusetts, United States, 02130 United States, North Carolina Duke University Durham, North Carolina, United States, 27705 United States, Tennessee Vanderbilt University Medical Center Nashville, Tennessee, United States, 37212 United States, Texas Baylor College of Medicine Lester and Sue Smith Breast Center Houston, Texas, United States, 77030 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.72mL

0.34mL

0.17mL

8.60mL

1.72mL

0.86mL

17.21mL

3.44mL

1.72mL
参考文献

[1]Rusnak DW, Lackey K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.

[2]Wood ER, Truesdale AT, et al. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 2004 Sep 15;64(18):6652-9.

[3]ASSESSMENT REPORT FOR TYVERB

[4]Pharmacokinetics of lapatinib