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EGFR-IN-2
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
EGFR-IN-2图片
规格:98%
分子量:551.66
包装与价格:
包装价格(元)
250mg电议
500mg电议

产品介绍
EGFR-IN-2是一种非共价的,不可逆的,突变选择性的二代EGFR抑制剂。
货号:ajcx12894
CAS:1643497-70-4
分子式:C26H33N9O3S
分子量:551.66
溶解度:Soluble in DMSO
纯度:98%
存储:Store at -20°C
库存:现货

Background:

EGFR-IN-2 is a a noncovalent, irreversible, mutant-selective second generation EGFR inhibitor.

EGFR-IN-2 (Compound 21) inhibits EGFR autophosphorylation with IC50s of 0.027 μM, 0.009 μM ,0.033 μM , and 0.218 μM in double mutant TMLR cell line H1975, double mutant TMdel cell line PC9-ER, activating mutant del70% when tested at 0.1 μM, 61-fold over the TMLR Ki and 63-fold over the TMdel Ki)[1].

To examine its inhibitory effect on pEGFR levels in vivo, EGFR-IN-2 (Compound 21) is studied in a mouse H1975 (TMLR) xenograft model. After a single oral dose of 21 at 50 mg/kg, free plasma concentrations of EGFR-IN-2 at or exceeding the in vitro p-EGFR IC50 of 0.027 μM are sustained over 8 h. When administered at 100 mg/kg, the coverage of p-EGFR IC50 is extended to the last measured time point of 16 h postdose. Corresponding knockdown of p-EGFR and the downstream effectors pERK1/2 and AKT levels are observed at those time points, suggesting target engagement in vivo. In mouse, after intravenous and oral administration, the plasma clearance of EGFR-IN-2 is determined to be 104 mL/kg per min with a bioavailability of 19%. In dogs, the plasma clearance is 13 mL/kg per min with an oral bioavailability of 30%[1].

[1]. Chan BK, et al. Discovery of a Noncovalent, Mutant-Selective Epidermal Growth Factor Receptor Inhibitor. J Med Chem. 2016 Oct 13;59(19):9080-9093.

Protocol:

Animal experiment:

Mice[1]Eight week old female SCID beige mice are inoculated subcutaneously with 5×106 NCI-H1975 cells. When tumors reach a mean volume of 300 to 500 mm3, mice with similarly sized tumors are randomized into treatment groups. EGFR-IN-2 at 50 mg/kg or 100 mg/kg is administered orally as a single dose. Tumor and plasma samples are collected at 2, 8 or 16 h post dose[1].

参考文献:

[1]. Chan BK, et al. Discovery of a Noncovalent, Mutant-Selective Epidermal Growth Factor Receptor Inhibitor. J Med Chem. 2016 Oct 13;59(19):9080-9093.