Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies

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• 作者：Fenlai Tan^a ; ¹ ; Xiaoyan Shen^a ; ¹ ; Dechang Wang^b ; Guojian Xie^c ; Xiaodong Zhang^c ; Lieming Ding^a ; Yunyan Hu^a ; Wei He^a ; Yanping Wang^a ; Yinxiang Wang^a ; ^{shenxiaoyan1002@126.com} ; ^{yinxiang.wang@betapharma.com.cn}
• 关键词：EGFR&ndash ; TKIs ; Icotinib ; NSCLC ; In vivo ; EGFR mutation
• 刊名：Lung Cancer
• 出版年：2012
• 期刊代码：187_01695002
• 类别：med
• 出版时间：May, 2012
• 卷：76
• 期：2
• 页码：177-182
• 文件大小：580 K

摘要

Icotinib, one of the leading compounds selected from our compound library, was found to be a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an IC₅₀ of 5 nM. When profiled with 88 kinases, Icotinib only showed meaningful inhibitory activity to EGFR and its mutants. Icotinib blocked EGFR-mediated intracellular tyrosine phosphorylation (IC₅₀ = 45 nM) in the human epidermoid carcinoma A431 cell line and inhibits tumor cell proliferation. In vivo studies demonstrated that Icotinib exhibited potent dose-dependent antitumor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug was well tolerated at doses up to 120 mg/kg/day in mice without mortality or significant body weight loss during the treatment. A head to head randomized, double blind phase III trial using Gefitinib as an active control for patients with advanced non-small cell lung cancer (NSCLC) was finished recently (Trial registration ID: ). The data shows that Icotinib was non-inferior to Gefitinib in terms of median progression free survival (PFS) and safety superior favor to Icotinib compared to Gefitinib.