Lapatinib Ditosylate
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 Ditosylate是ErbB-2和EGFR的双重选择性抑制剂,体外实验中,ErbB-2和EGFR的IC50值分别为9.2和10.8 nM[1]。
EGFR和ErbB-2都是I型酪氨酸激酶受体,分布在细胞表面,被确认为抗癌的潜在靶标。配体与受体特异性结合引起受体的构象变化,随后激活激酶结构域。ErbB-2没有已知的直接激活的配体,可与其它结合配体的家庭成员形成异二聚体进行活化。EGFR二聚化激活酪氨酸激酶活性,并通过其它几种蛋白引发下游信号传导,这些蛋白启动多个信号转导通路。EGFR和ErbB-2通过Ras通路来刺激细胞分裂,并通过PI3K途径导致细胞生长[1]。
Lapatinib是ErbB-2和EGFR的选择性抑制剂。与其它激酶相比,例如MEK和ERK,Lapatinib对ErbB-2和EGFR 的选择性大于300倍。Lapatinib可与细胞内ATP竞争结合Erb-2和EGFR,随后抑制它们的活化。在细胞增殖实验中,Lapatinib抑制人肿瘤细胞的生长。在ErbB-2和EGFR 过表达细胞系HN5和A-431中,IC50值小于0.16 nM。在低表达ErbB-2和EGFR的细胞系中的IC50值比过表达的细胞系高约25倍。10 nM的Lapatinib导致HN5细胞的G1期阻滞。在ErbB-2过表达细胞系中,5 nM Lapatinib可100%完全抑制Erk1/2的磷酸化。1 nM Lapatinib Ditosylate抑制EGF刺激的Erk1 / 2和AKT的磷酸化[1,2]。
在人乳腺癌异种移植小鼠中,每日两次75 mg/ kg的lapatinib在21天导致肿瘤体积显著变小[3]。100 mg/kg的剂量每日两次完全抑制HN5和BT474人肿瘤异种移植肿瘤的生长[1]。
参考文献:
1. Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ 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, 1(2):85-94.
2.Xia W, Mullin RJ, Keith BR, Liu LH, Ma H, Rusnak DW, Owens G, Alligood KJ, Spector NL: Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 2002, 21(41):6255-6263.
3.Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, Untch M, Rusnak DW, Spehar G, Mullin RJ et al: Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006, 66(3):1630-1639.
Physical Appearance | A solid |
Storage | Store at RT |
M.Wt | 925.46 |
Cas No. | 388082-77-7 |
Formula | C29H26ClFN4O4S 2C7H8O3S |
Synonyms | Tykerb Ditosylate |
Solubility | ≥24.3 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-amine bis(4-methylbenzenesulfonate) |
SDF | Download SDF |
Canonical SMILES | O=S(CCNCC1=CC=C(C2=CC3=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)N=CN=C3C=C2)O1)(C)=O.O=S(C6=CC=C(C)C=C6)(O)=O.O=S(C7=CC=C(C)C=C7)(O)=O |
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。 |
描述 | Lapatinib Ditosylate(GW572016,GW2016)是EGFR和ErbB2的有效抑制剂,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
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