Powder: -20°C for 3 years | In solvent: -80°C for 1 year
EAI045是突变体EGFR 的变构抑制剂,在10 μM ATP 时抑制EGFR、EGFRL858R、EGFRT790M 和 EGFRL858R/T790M 的IC50值分别为1.9、0.019、0.19 和 0.002 μM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
10 mg | ¥ 491 | 现货 | ||
50 mg | ¥ 1,255 | 现货 | ||
100 mg | ¥ 1,997 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 377 | 现货 |
产品描述 | EAI045, an allosteric inhibitor, targets towards drug-resistant EGFR mutants but avoids the wild-type receptor. |
靶点活性 | EGFR (T790M):0.19 μM, EGFR:1.9 μM, EGFR (L858R):0.002 μM, EGFR (L858R):0.019 μM |
体外活性 | EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (half maximal effective concentration (EC50)=2 nM), but not in HaCaT cells, a keratinocyte cell line with wild-type EGFR. Despite potent inhibition of mutant EGFR, EAI045 shows no anti-proliferative effect in the H1975 and H3255 cell lines with concentrations as high as 10 μM[1]. EAI045 inhibits L858R/T790M mutant with an IC50 of 3 nM. However, EAI045 is not able to completely abolish EGFR autophosphorylation in H1975 NSCLC cell line harboring the L858R/T790M mutant. Dimerization-defective/independent mutants are markedly more sensitive to EAI045. Since EGFR dimerization is required for kinase enzyme activation, EAI045 may be active against one subunit of an EGFR heterodimer/asymmetric dimer[2]. |
体内活性 | Mouse pharmacokinetic studies with EAI045 reveals a maximal plasma concentration of 0.57 μM, a half-life of 2.15 h, and oral bioavailability of 26% after dosing at 20 mg/kg[1]. When combined with cetuximab that blocks EGFR dimerization, EAI045 markedly reduces tumor growth in a mouse model of L858R/T790M-mutant-driven lung cancer. The mice treated alone with EAI045 do not respond. EAI045 in combination with cetuximab also induces marked tumor shrinkage in the mouse model carrying L858R/T790M/C797S, a mutant known to be resistant to all third-generation EGFR TKIs. EAI045 and cetuximab exhibits mechanistic synergy[2]. |
激酶实验 | ERK dimerization assay: Compound screening is performed in HEK293T cells treated with the potential inhibitors (10 μM) for 30 min before EGF stimulation. Cellular lysates are tested for ERK dimerization by native PAGE and p-ERK evaluation of the potential positives. In vitro ERK dimerization is assayed using GST-MEK1 ΔN EE purified from bacteria, bound to glutathione sepharose beads, and incubated with 25 μg/ml of purified His-ERK2 plus increasing concentrations of DEL-22379. Western blotting, kinase assays, and luciferase assays are also performed. In silico docking of the DEL-22379 compound is carried out with the modeling tools provided by the OpenEye package (v. 2.1). |
细胞实验 | H1975, H3255 and HaCaT cell lines are plated in solid white 384-well plates at 500 cells per well in 10% FBS RPMI penicillin/streptomycin media. Using a Pin Tool, 50 nl of serial diluted compounds are transferred to the cells. After 3?days, cell viability is measured.(Only for Reference) |
分子量 | 383.4 |
分子式 | C19H14FN3O3S |
CAS No. | 1942114-09-1 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 71 mg/mL (185.2 mM)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
H2O: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.6082 mL | 13.0412 mL | 26.0824 mL | 65.2061 mL |
5 mM | 0.5216 mL | 2.6082 mL | 5.2165 mL | 13.0412 mL | |
10 mM | 0.2608 mL | 1.3041 mL | 2.6082 mL | 6.5206 mL | |
20 mM | 0.1304 mL | 0.6521 mL | 1.3041 mL | 3.2603 mL | |
50 mM | 0.0522 mL | 0.2608 mL | 0.5216 mL | 1.3041 mL | |
100 mM | 0.0261 mL | 0.1304 mL | 0.2608 mL | 0.6521 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
EAI045 1942114-09-1 Angiogenesis JAK/STAT signaling Tyrosine Kinase/Adaptors EGFR Inhibitor Epidermal growth factor receptor ErbB-1 EAI 045 inhibit HER1 EAI-045 inhibitor