title: F84, a quinazoline derivative, exhibits high potent antitumor activity against human gynecologic malignancies.
abstract: EGFR overexpression in gynecologic cancer has been associated with poor prognosis. Targeted inhibition of EGFR via its tyrosine kinase domain is a successful treatment in lung cancer. However, the results of existing clinical trials in gynecologic cancers do not show a significant clinical response to EGFR inhibition alone in unscreened patients. Novel EGFR-TKI might be beneficial for patients with gynecologic cancers. In this article, the in vitro and in vivo effects of a newly synthesized novel EGFR tyrosine kinase inhibitor N-(3-bromophenyl)-N-(7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-yl)-3,3-dimethylbutanamide (F84) is being reported. In vitro, F84 and PD153035 significantly inhibited the growth of four different human gynecologic cancer cell lines in a dose-dependent manner. In vivo, F84 exhibited an inhibitory effect on gynecologic malignancies. While the mechanism of action is still unclear, it might be related to inhibition of EGFR signaling pathway, delay in cell cycle progression and a G1 arrest together with a partial G2/M block and induction of apoptosis. These results suggest that F84 could be a potential drug candidate for the treatment of human gynecologic malignancies.
authors.affiliation: Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xian Nong Tan Street, Beijing 100050, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Meng
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
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; D001835:Body Weight / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C550331:N-(3-bromophenyl)-N-(7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-yl)-3,3-dimethylbutanamide; D011799:Quinazolines; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline