埃罗替尼 T0373

Product Introduction
Bioactivity


英文名: Erlotinib

描述: Erlotinib (NSC-718781) 是一种直接作用的EGFR 酪氨酸激酶抑制剂，用于治疗非小细胞肺癌，对人 EGFR 的IC50为 2 nM。它可降低完整肿瘤细胞的 EGFR 自磷酸化，IC50为 20 nM。

细胞实验: Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib (30 nM-20 μM), 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 the drug(s) compared with untreated control cells and is calculated by the CalcuSyn software [4].

激酶实验: 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 anti-phosphotyrosine antibody, diluted to 0.2 μg/mL in blocking buffer (3% BSA and 0.05% Tween 20 in PBS). The antibody is removed by aspiration, and the plate is washed 4 times with washing buffer. The colorimetric 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 background in wells without AlP, EGFR, or PGT and is proportional to the time of incubation for 10 minutes [1].

动物实验: Six-week-old male SD rats weighing 180 to 210 g are used. Cisplatin (CP) is freshly prepared in saline at a concentration of 1 mg/mL and then injected intraperitoneally in SD rats (n=28) at a dose of 7 mg/kg on day 0. To investigate the effect of Erlotinib, 28 CP-N rats are divided into two groups. Separate groups (n=14) each of animals are administered with either Erlotinib (20 mg/kg) (CP+E, n=14) or vehicle (CP+V, n=14) daily by oral gavage from the day -1 (24 hours prior to the CP injection) to day 3. Vehicle-treated groups receive an equivalent volume of saline. Five male SD rats at the age of 6 weeks are used as a normal control group (NC, n=5). The NC rats are given an equivalent volume of saline daily by oral gavage from the day -1 to day 3. At day 4 (96 hours after CP injection), each rat is anesthetized and sacrificed by exsanguination after the cardiac puncture; blood is collected by cardiac puncture and kidneys are collected. Renal tissue is divided; separate portions are snap-frozen in liquid nitrogen or fixed in 2% paraformaldehyde/phosphate-buffered saline (PBS) for later use. All surgery is performed under diethyl ether gas anesthesia, and all efforts are made to minimize suffering [2].

体外活性: Erlotinib 是一种针对人类EGFR酪氨酸激酶的抑制剂（其IC50为2 nM），能在完整肿瘤细胞中降低EGFR自磷酸化（IC50为20 nM）。Erlotinib 也是重组内源性（激酶）结构域EGFR的强效抑制剂，IC50为1 nM。Erlotinib 还能强烈抑制DiFi细胞的增殖，在8天的增殖实验中IC50为100 nM[1]。

体内活性: 与CP+载体(V)组相比，Erlotinib（20 mg/kg, 口服）显著减轻顺铂(CP)诱导的大鼠体重(BW)损失。Erlotinib 治疗显著改善CP-N（正常对照组，NC）大鼠的肾功能。与CP+V组相比，CP+E组大鼠的血清肌酐(s-Cr)水平、血尿素氮(BUN)、尿N-乙酰-β-D-葡萄糖胺酶(NAG)指数均显著减少（P<0.05），尿量(UV)和肌酐清除率(Ccr)显著增加（P<0.05）[2]。Erlotinib 抑制小鼠体内人头颈部癌HN5肿瘤移植瘤的生长，ED50为9 mg/kg[3]。

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 60 mg/mL (152.5 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 12 mg/mL (30.5 mM)


关键字: ErbB-1 | CP 358774 | cancer | tumor | acting | OSI-774 | inhibit | CP-358774 | OSI 774 | Inhibitor | EGFR | Autophagy | Erlotinib | OSI774 | directly | NSC-718781 | R 1415 | intact | HER1 | cell | autophosphorylation | OSI744 | R-1415 | Epidermal growth factor receptor | lung | non-small | OSI 744 | NSC718781

相关产品: EGFR/ErbB-2 inhibitor-1 | Neratinib maleate | Hirsutenone | PP2 | Boehmenan | Ligustroside | SYR127063 | Sulforaphene | (S)-Sunvozertinib | TAS6417

相关库: Drug Repurposing Compound Library | Anti-Cancer Drug Library | Anti-Cancer Clinical Compound Library | Kinase Inhibitor Library | Inhibitor Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Approved Drug Library | Anti-Cancer Active Compound Library | Highly Selective Inhibitor Library | EMA Approved Drug Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途