F84, a quinazoline derivative, exhibits high potent antitumor activity against human gynecologic malignancies.

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.