title: Anti-tumor activity of a novel EGFR tyrosine kinase inhibitor against human NSCLC in vitro and in vivo.
abstract: Epidermal growth factor receptor (EGFR) is highly expressed in many human tumors including non-small cell lung cancer (NSCLC). Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has led to dramatic clinical improvement in selected patients with NSCLC. However, intrinsic and acquired resistance to EGFR-TKI remains a common phenomenon. Novel EGFR-TKI, structurally different with erlotinib or gefitinib might be beneficial for patients with NSCLC. In this study, we examined the anti-tumor effect of a newly synthesized novel EGFR tyrosine kinase inhibitor N-(3-chloro-4-fluorophenyl)-N-(7-methoxy-6-(3-morpholinopropoxy) quinazolin-4-yl)-3,3-dimethylbutanamide (F90). In vitro studies in a panel of three different human NSCLC cell lines revealed that F90 inhibited cell proliferation with high potency and induced G0/G1 arrest of cell cycle and apoptosis. F90 markedly reduced phosphorylation of EGFR and inhibited activation of MAPK and Akt. Oral administration of F90 (80mg/kg/day) to BALB/c nude mice bearing NSCLC cell lines xenografts significantly retarded tumor growth. In conclusion, F90 has potent anti-tumor activity on human lung cancer in vitro and in vivo.
authors.affiliation: Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xian Nong Tan Street, Beijing 100050, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Feng
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C533668:F90 compound; D011799:Quinazolines; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000077156:Gefitinib