WB-308, A Novel Inhibitor Of EGFR, Suppresses The Growth Of Non-small Cell Lung Cancer (NSCLC)

Non-small lung cancer (NSCLC) is the leading cause of cancer death in the worldwide. The epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family, which play important roles in the development of NSCLC. EGFR and its downstream signaling pathways are excessively activated in 40-80% of NSCLC patients. Therefore, drug development targeting EGFR is an encouraging strategy for NSCLC treatment.In our study, in order to identify inhibitors targeting to kinase activity of EGFR in NSCLC, WB-308, a small molecular compound with molecular weight 308, has been identified through screening and tested the molecular interaction by the molecular docking modeling assay and EGFR kinase activity assay in vitro. Results showed that WB-308 binds with EGFR activity sites and inhibited the activity of EGFR kinase. Second, NSCLC cell lines (HCC-827, NCI-H1650, SPC-A1, A549, NCI-H1975) were treated with WB-308, results showed that WB-308 inhibited the proliferation of NSCLC cell lines, suppressed the cloning formation of SPC-A1 cell, bloked the cell-cycle of PC-9 cell at G2/M phase, induced the apoptosis of NSCLC cell lines in a concentration-dependent manner. Furthermore, two different in vivo animal models (lung orthotopic transplantation model and Xenograft mouse model) were used. The date showed that WB-308 suppressed the tumor growth. Finally, WB-308 reduced the phosphorylation level of EGFR, AKT, ERK1/2 protein significantly.In summary, WB-308 is a novel EGFR-TKI by blocking EGFR signaling pathways and WB-308 could be a potential agent for the treatment of NSCLC.