title: Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies.
abstract: 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.
authors: Zhejiang Beta Pharma Inc., R&D Center, 1 North Disheng St., 29, BPUSP, Beijing 100176, China.
authors: Fenlai
authors: F
authors: Tan
authors: Xiaoyan
authors: X
authors: Shen
authors: Dechang
authors: D
authors: Wang
authors: Guojian
authors: G
authors: Xie
authors: Xiaodong
authors: X
authors: Zhang
authors: Lieming
authors: L
authors: Ding
authors: Yunyan
authors: Y
authors: Hu
authors: Wei
authors: W
authors: He
authors: Yanping
authors: Y
authors: Wang
authors: Yinxiang
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D043844:Crown Ethers / Q000494:pharmacology*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D043844:Crown Ethers; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014443:Tyrosine; C531470:icotinib; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib