印度厄洛替尼

产品描述

Erlotinib is an EGFR inhibitor (IC50: 2 nM). It is used for the treatment of non-small cell lung cancer.

靶点活性

EGFR/HER1,2nM

实验溶液

15% Captisol: 16 mg/mL warmed

体外活性

Erlotinib（10 uM）抑制EGFR在Y1068(自磷酸化) 和Y845 (Src依赖性磷酸化) 位点磷酸化。Erlotinib不影响SBC-5细胞增殖，但是以剂量依赖的方式明显抑制PC-9细胞（在EGFR基因第19外显子含缺失突变）增殖。Erlotinib对SBC-5细胞迁移也没有作用。Erlotinib抑制Capan-1细胞和HPAC细胞生长， IC50 分别为3和1.1μM。Erlotinib作用于HNS人颈部和头部肿瘤细胞，能明显抑制EGFR自磷酸化，上述肿瘤细胞是EGFR高表达的细胞系。只有作用于最敏感的细胞株时，Erlotinib才能抑制细胞外信号调节激酶Akt和S6。

体内活性

单独作用于H460a肿瘤模型时，Erlotinib以剂量依赖性方式抑制肿瘤生长，且与药物循环水平相关。

激酶实验

Kinase assays: 96-well plates are coated by incubation overnight at 37 °C with 100 μL per well of 0.25 mg/mL PGT in PBS. Excess PGT is removed by aspiration, and the plate is washed 3 times with washing buffer (0.1% Tween 20 in PBS). The kinase reaction is performed in 50 μL of 50 mM HEPES (pH 7.3), containing 125 mM sodium chloride, 24 mM magnesium chloride, 0.1 mM sodium orthovanadate, 20 μM ATP, 1.6 μg/mL EGF, and 15 ng of EGFR, affinity purified from A431 cell membranes. Erlotinib HCl in DMSO is added to give a final DMSO concentration of 2.5%. Phosphorylation is initiated by addition of ATP and proceeded for 8 minutes at room temperature, with constant shaking. The kinase reaction is terminated by aspiration of the reaction mixture and is washed 4 times with washing buffer. Phosphorylated PGT is measured by 25 minutes of incubation with 50 μL per well HRP-conjugated PY54 antiphosphotyrosine antibody, diluted to 0.2 μg/mL in blocking buffer (3% BSA and 0.05% Tween 20 in PBS). Antibody is removed by aspiration, and the plate is washed 4 times with washing buffer. The colonmetric signal is developed by addition of TMB Microwell Peroxidase Substrate, 50μL per well, and stopped by the addition of 0.09 M sulfuric acid, 50 μL per well. Phosphotyrosine is estimated by measurement of absorbance at 450 nm. The signal for controls is typically 0.6-1.2 absorbance units, with essentially no back ground in wells without AlP, EGFR, or PGT and is proportional to the time of incubation for 10 minutes.

细胞实验

Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib, pemetrexed, or the combination at a constant concentration ratio of 4:1 in triplicates for 72 h. Cell viability is assayed by cell count and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Growth inhibition is expressed as the percentage of surviving cells in drug-treated versus PBS-treated control cells (which is considered as 100% viability). The IC50 value is the concentration resulting in 50% cell growth inhibition by a 72-h exposure to drug(s) compared with untreated control cells and is calculated by the CalcuSyn software.(Only for Reference)

细胞系： A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 cells

动物实验

动物模型：5-week-old BALB-nu/nu with HPAC cells

分子量

429.90

分子式

C22H23N3O4·HCl

CAS

183319-69-9

溶解度

DMSO: 9.3 mM

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.