Inhibition of non-small cell lung cancer (NSCLC) growth by a novel small molecular inhibitor of EGFR.
The epidermal growth factor receptor (EGFR) is a therapeutic target (oncotarget) in NSCLC. Using in vitro EGFR kinase activity system, we identified a novel small molecule, WB-308, as an inhibitor of EGFR. WB-308 decreased NSCLC cell proliferation and colony formation, by causing G2/M arrest and apoptosis. Furthermore, WB-308 inhibited the engraft tumor growths in two animal models in vivo (lung orthotopic transplantation model and patient-derived engraft mouse model). WB-308 impaired the phosphorylation of EGFR, AKT, and ERK1/2 protein. WB-308 was less cytotoxic than Gefitinib. Our study suggests that WB-308 is a novel EGFR-TKI and may be considered to substitute for Gefitinib in clinical therapy for NSCLC.
['Li|Jinsong|J|', 'Deng|Huayun|H|', 'Hu|Meichun|M|', 'Fang|Yuanzhang|Y|', 'Vaughn|Amanda|A|', 'Cai|Xiaopan|X|', 'Xu|Leqin|L|', 'Wan|Wei|W|', 'Li|Zhenxi|Z|', 'Chen|Shijie|S|', 'Yang|Xinghai|X|', 'Wu|Song|S|', 'Xiao|Jianru|J|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D002243:Carbolines D002289:Carcinoma, Non-Small-Cell Lung D045744:Cell Line, Tumor D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D066246:ErbB Receptors D059565:G2 Phase Cell Cycle Checkpoints D000077156:Gefitinib D006801:Humans D008175:Lung Neoplasms D008819:Mice, Nude D019950:Mitogen-Activated Protein Kinase 1 D048052:Mitogen-Activated Protein Kinase 3 D062105:Molecular Docking Simulation D058990:Molecular Targeted Therapy D009154:Mutation D010766:Phosphorylation D011487:Protein Conformation D047428:Protein Kinase Inhibitors D051057:Proto-Oncogene Proteins c-akt D011799:Quinazolines D015398:Signal Transduction D013997:Time Factors D014162:Transfection D047368:Tumor Burden D023041:Xenograft Model Antitumor Assays
NSCLC EGFR tumor growth TKIs