EGFR抑制剂 曲妥珠单抗(Trastuzumab)CAS:231277-92-2 Lapatinib 拉帕替尼

Lapatinib 拉帕替尼; GW572016;GSK 572016;ErbB2抑制剂;EGFR抑制剂;曲妥珠单抗(Trastuzumab);CAS:231277-92-2;

产品信息                                                                                                            

产品名称 产品编号 CAS NO. 规格
Lapatinib拉帕替尼 MZ20306-50MG 231277-92-2 50mg
Lapatinib拉帕替尼 MZ20306-100MG 231277-92-2 100mg 5
Lapatinib拉帕替尼 MZ20306-1G 231277-92-2 1g

拉帕替尼(Lapatinib),又称为GW572016、GSK 572016,是一种有效的ErbB2和EGFR抑制剂,在无细胞试验中IC50分别为9.2和10.8nM。除掉ErbB4(IC50=367nM)之外,拉帕替尼对ErbB2和EGFR的选择性比其他测试激酶>300倍[1]。拉帕替尼抑制EGFR过表达的A431皮肤癌细胞和ErbB2过表达的SK-BR-3乳腺癌细胞生长(IC50s分别是0.14和0.124μM)。还能抑制ErbB2扩增的OD19食道癌和NCI-N87胃癌细胞生长(IC50s分别是0.09和0.01μM)以及一系列ErbB2并未扩增表达的胃癌细胞生长(IC50s = 0.35-8.58μM)[2]。拉帕替尼(1μM)诱导NCI-N87和OD19细胞的凋亡,拉帕替尼(50mg/kg)能降低BT474乳腺癌肿瘤移植瘤模型的肿瘤生长[3]。拉帕替尼(100mg/kg)能够减少NCI-N87小鼠移植瘤模型的肿瘤生长,当与曲妥珠单抗(Trastuzumab)联合使用能诱导肿瘤缩小[1]。

产品特性

1)  CAS NO:231277-92-2

2)  化学名:N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[[[2-(methylsulfonyl)ethyl]amino]methyl]-2- furanyl]-4-quinazolinamine

3)   同义名:GW 572016, GW-572016, GSK 572016, GSK-572016, GD 2016, Tykerb; 泰立沙;

4)   分子式:C29H26ClFN4O4S

5)   分子量:581.06

6)   纯度:≥98%

7)   溶解性:溶于DMSO(≥20 mg/mL)

8)   化学结构式:

保存与运输方法

保存:-20℃干燥保存,至少3年有效。

运输:室温运输。

注意事项

1)   关于化合物溶解性的一般建议:为了更好的溶解,可置于37℃加热或/和超声波震荡片刻的方式。不同厂家不同批次产品的溶解度会有差异,仅做参考。实验中所需浓度过大至溶解极限,需添加助溶剂或调整浓度方式来满足实验需求。

2)   本品仅用作科研用途,不得用作临床诊断或治疗,不得用于食品或药品,绝对禁止用在人身上。

3)   为了您的安全和健康,请穿实验服并戴一次性手套操作。

配制储存液

         质量     

溶剂体积

浓度

1mg              5mg              10mg             100mg          
1mM 1.7210 mL 8.6050 mL 17.2099 mL 172.0993 mL
5mM 0.3442 mL 1.7210 mL 3.4420 mL 34.4199 mL
10mM 0.1721 mL 0.8605 mL 1.7210 mL 17.2099 mL
50mM 0.0344 mL 0.1721 mL 0.3442 mL 3.4420 mL

使用方法【源自文献,仅作参考】

文献1,Rusnak DW 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. PMID: 12467226

体外研究:

细胞类型(Cell type):EGFR-overexpressing cell lines HN5, ErbB-2-overexpressing cell lines BT474, Normal human foreskin fibroblasts (HFF)

药物配制(Preparation):GW2016 was dissolved in DMSO

实验方法(Assay):Cells are plated in 96-well plates in the media at the following densities: HFF and HN5, 1000 cells/well and BT474, 5000 cells/well.After 24 h, the cells are exposed to vehicle (0.3% DMSO) or Lapatinib (1 nM, 10 nM, 100 nM, 1μM, 10μM, and 100μM).Lapatinib is removed from the cells after 72 h and is replaced by either DMEM containing 10% FBS and 50 μg/mL Gentamicin (HFF and HN5) or RPMI containing 10% FBS and 50 μg/mL Gentamicin (BT474). Methylene blue staining is performed at the time points over a total period of 16 day.

体内研究:

动物模型(Animal Model):BT474 human tumor xenografts (established in C.B-17 SCID female mice), HN5 human tumor xenografts (established in CD-1 nude female mice)

药物配制(Preparation):GW2016 was dissolved in a vehicle of sulfo-butyl-ether-β-cyclodextrin 10% aqueous solution.

给药剂量(Dosages):Experimental compounds (30mg/kg and 100mg/kg) were administered p.o. twice daily for 21 days in a vehicle of sulfo-butyl-ether-β-cyclodextrin 10% aqueous solution.

实验结果(Results):GW2016 was potent at inhibiting the growth of BT474 and HN5 human tumor xenografts. A dose-responsive inhibition of both models occurred on treatment of tumor-bearing mice with 30 and 100 mg/kg GW2016 orally, twice daily. Complete inhibition of tumor growth was seen at the 100 mg/kg dose.

文献2,Wainberg ZA et al. 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 Mar 1;16(5):1509-19. PMID: 20179222

体外研究:

细胞类型(Cell type):14 established human gastric and esophageal cancer cell lines that express variable levels of EGFR and HER2: AGS, NCI-N87, KATO III, SNU-1, SNU-5, and SNU-16; NUGC4, NUGC3, FU97, IM95, IM95m, MKN74, and MKN1; OE19;

药物配制(Preparation):Lapatinib was prepared as a 10 mmol/L stock solution in DMSO.

实验方法(Assay):Cells were plated into 24-well plates at a density of 2 × 104to 6 × 104and grown in cell line– specific medium in decreasing concentrations of both lapatinib (ranging between 10 and 0.3125 μM) and erlotinib (ranging between 10 and 0.3125 μM). The same cell lines were treated with trastuzumab at a fixed dose of 10 μg/mL. Cells were harvested by trypsinization on day 6 and counted using a particle counter.

体内研究:

动物模型(Animal Model):N87-bearing xenografts

药物配制(Preparation):Lapatinib was dissolved in 0.5% hydroxypropyl methylcellulose (HPMC) with 0.1% Tween 80.

注射剂量(Dosages):N87 cells (5×106cells with 50% Matrigel) were injected s.c. into nude mice and mice were randomized into one of four groups (n = 11/group).Treatment started at day 4 after injection with either lapatinib (100 mg/kg daily for 3 wkby oral gavage in 0.5% hydroxypropyl methylcellulose and 0.1% Tween 80),trastuzumab (10 mg/kgin sterile PBS,i.p. twice weekly) or sterile PBS (i.p. twice weekly) or the combination of lapatinib and trastuzumab at the doses above. Tumors were measured biweekly. After 23 d of treatment, the animals were euthanized.

实验结果(Results):Both single-agent lapatinib and trastuzumab caused tumor regression in N87 xenografts. In addition, the combination showed near complete tumor resolution by day 23.

参考文献

[1] Rusnak DW 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] Wainberg ZA et al. 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 Mar 1;16(5):1509-19.

[3] Chefrour M et al. Positive interaction between lapatinib and capecitabine in human breast cancer models: Study of molecular determinants. Fundam Clin Pharmacol. 2012 Aug;26(4):530-7.

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