Lapatinib
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Lapatinib也称为GW572016,是4-苯胺基类激酶抑制剂的成员,是一种有效的、选择性的和可逆的表皮生长因子受体(EGFR)和人表皮生长因子受体2(HER-2)酪氨酸激酶小分子抑制剂。在无细胞生化激酶试验中,Lapatinib抑制重组EGFR和HER-2酪氨酸激酶,IC50值分别为10.8 nmol/L 和9.3 nmol/L。Lapatinib干扰三磷酸腺苷结合于EGFR 和HER-2的酪氨酸激酶结构域,从而抑制自磷酸化和下游信号活动的产生,比如细胞增殖和存活[1-3]。
参考文献:
[1] Alison Reid, Laura Vidal, Heather Shaw and Johann de Bono. Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). European Journal of Cancer 43 (2007) 481-489.
[2] Norio Kondo, Mamoru Tsukuda, Yukari Ishiguro, Machiko Kimura, Kyoko Fujita, Atsuko Sakakibara, Hideaki Takahashi, Gabor Toth and Hideki Matsuda. Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma. Oncology Reports 23: 957-963, 2010.
[3] Zev A. Wainberg, Adrian Anghel, Amrita J. Desai, Raul Ayala, Tong Luo, Brent Safran, Marlena S. Fejzo, J. Randolph Hecht, Denni J. Slamon and Richard S. Finn. Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo. Clin Cancer Res 2010; 16(5): 1509-1519.
- 1. Lee YC, Wang LJ, et al. "Inhibition of EGFR pathway promotes the cytotoxicity of ABT-263 in human leukemia K562 cells by blocking MCL1 upregulation." Biochem Pharmacol. 2020;178:114047. PMID:32446890
- 2. Ying Z, Beronja S. "Embryonic Barcoding of Equipotent Mammary Progenitors Functionally Identifies Breast Cancer Drivers." Cell Stem Cell. 2020;S1934-5909(20)30009-6. PMID:32059806
- 3. Neal Shah, Pharm.D. "Investigational Chemotherapy and Novel Pharmacokinetics for the Treatment of Cancers of the CNS." West Virginia University. 2019.
- 4. Duggan BM, Foley KP, et al. "Tyrosine kinase inhibitors of Ripk2 attenuate bacterial cell wall-mediated lipolysis, inflammation and dysglycemia." Sci Rep. 2017 May 8;7(1):1578. PMID:28484277
- 5. Zhang WJ, Li Y, et al. "Synergistic antitumor activity of regorafenib and lapatinib in preclinical models of human colorectal cancer." Cancer Lett. 2017 Feb 1;386:100-109. PMID:27864115
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 581.06 |
Cas No. | 231277-92-2 |
Formula | C29H26ClFN4O4S |
Synonyms | Tykerb;GW572016;GW-572016;GW 572016, Lapatinib tosilate hydrate |
Solubility | ≥29.05 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine |
SDF | Download SDF |
Canonical SMILES | CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验 [1]: | |
结合实验 |
从杆状病毒表达系统纯化EGFR、ErbB-2和ErbB4的细胞内激酶结构域。EGFR、ErbB-2和ErbB-4反应在最终体积为45 μl的96孔聚苯乙烯圆底板中进行。反应混合物含有50 mM 4-吗啉基丙磺酸(pH7.5)、2 mM MnCl2、10 μM ATP、1μCi[γ-33P] ATP/反应,50 μM肽A [生物素-(氨基己酸)-EEEEYFELVAKKK-CONH2]、1 mM二硫苏糖醇和1 μl 含有连续稀释GW2016(起始浓度为10 μM)的DMSO。加入纯化的1型受体细胞内结构域引发反应。酶的量为1 pmol/反应(20 nM)。在23℃下孵育10分钟后,加入45 μl的0.5%磷酸水溶液终止反应。将终止的反应混合物(75 μl)转移到磷酸纤维素滤板上。将板过滤并用200 μl的0.5%磷酸洗涤三次。将闪烁混合物(50 μl)加入到每个孔中,通过在Packard Topcount中计数来定量测定。 |
细胞实验 [1]: | |
细胞系 |
EGFR过表达细胞系HN5和A-431,ErbB-2过表达细胞系BT474、N87(20)和CaLu-3 |
溶解方法 |
该化合物在DMSO中的溶解度大于29.1 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
30 μM,3天 |
应用 |
GW2016(30 μM)完全抑制HN5细胞群体的生长。GW2016(> 3.3 μM)抑制了50%的细胞生长。GW2016(0.37 μM)显著抑制了20%的生长。GW2016(1 μM)完全抑制了BT474细胞生长,0.37 μM浓度下产生约60%的生长抑制。在EGFR过表达细胞系HN5中,GW2016(1和10 μM)诱导G1停滞。GW2016(10 μM,72 h)轻微增加含有亚2N DNA含量的细胞数。在BT474细胞中,GW2016处理72小时后大幅增加具有亚2N DNA的细胞数量。 |
动物实验 [1]: | |
动物模型 |
BT474和HN5人肿瘤异种移植小鼠模型 |
给药剂量 |
口服,30和100 mg/kg,一天两次,持续21天 |
应用 |
Lapatinib (100 mg/kg) 完全抑制肿瘤生长。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Rusnak D W, Lackey K, Affleck 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[J]. Molecular cancer therapeutics, 2001, 1(2): 85-94. |
Description | Lapatinib是一种有效的EGFR和ErbB2抑制剂,IC50值分别为10.8和 9.2 nM。 | |||||
靶点 | EGFR | ErbB2 | ||||
IC50 | 10.8 nM | 9.2 nM |
质量控制和MSDS
- 批次: