Zhejiang Beta Pharma Inc., R&D Center, 1 North Disheng St., 29, BPUSP, Beijing 100176, China.
Lung Cancer. 2012 May;76(2):177-82. doi: 10.1016/j.lungcan.2011.10.023. Epub 2011 Nov 22.
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 IC(50) 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 (IC(50)=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: NCT01040780). 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.
从我们的化合物库中筛选出的先导化合物伊可替尼是一种有效的、特异性的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），其 IC50 为 5 nM。在对 88 种激酶进行分析时，伊可替尼仅对 EGFR 及其突变体显示出有意义的抑制活性。伊可替尼可阻断人表皮样癌细胞 A431 系中 EGFR 介导的细胞内酪氨酸磷酸化（IC50=45 nM），并抑制肿瘤细胞增殖。体内研究表明，伊可替尼在携带多种人源肿瘤衍生异种移植物的裸鼠中表现出强效的、剂量依赖性的抗肿瘤作用。在小鼠中，以高达 120mg/kg/天的剂量给药时，药物耐受性良好，在治疗期间无死亡或显著的体重减轻。一项以吉非替尼为活性对照的针对晚期非小细胞肺癌（NSCLC）患者的头对头、随机、双盲 III 期临床试验最近已完成（试验注册号：NCT01040780）。数据显示，伊可替尼在中位无进展生存期（PFS）方面不劣于吉非替尼，且安全性优于吉非替尼。
