In Vivo Anticancer Evaluation of 6b, a Non-Covalent Imidazo[1,2-]quinoxaline-Based Epidermal Growth Factor Receptor Inhibitor against Human Xenograft Tumor in Nude Mice.

Tyrosine kinase inhibitors are validated therapeutic agents against EGFR-mutated non-small cell lung cancer (NSCLC). However, the associated critical side effects of these agents are inevitable, demanding more specific and efficient targeting agents. Recently, we have developed and reported a non-covalent imidazo[1,2-]quinoxaline-based EGFR inhibitor (), which showed promising inhibitory activity against the gefitinib-resistant H1975(L858R/T790M) lung cancer cell line. In the present study, we further explored the compound in vivo by employing the A549-induced xenograft model in nude mice. The results indicate that the administration of the compound significantly abolished the growth of the tumor in the A549 xenograft nude mice. Whereas the control mice bearing tumors displayed a declining trend in the survival curve, treatment with the compound improved the survival profile of mice. Moreover, the histological examination showed the cancer cell cytotoxicity of the compound was characterized by cytoplasmic destruction observed in the stained section of the tumor tissues of treated mice. The immunoblotting and qPCR results further signified that inhibited EGFR in tissue samples and consequently altered the downstream pathways mediated by EGFR, leading to a reduction in cancer growth. Therefore, the in vivo findings were in corroboration with the in vitro results, suggesting that possessed potential anticancer activity against EGFR-dependent lung cancer. also exhibited good stability in human and mouse liver microsomes.