Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

• CIU1 was identified as novel lead compound for anticancer drug development.
• CIU1 was designed in silico by using a privilege scaffold from natural sources.
• CIU1 inhibited the growth of EGFR-overexpressing TNBC and NSCLC cells.
• CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells.
• CIU1 suppressed EGFR expression and induced programmed cell death.

A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido)vinyl)-1,2-phenylene diacetate (CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type non-small-cell lung cancer H460 cells with IC50 values of 8.96 μM and 12.98 μM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC50 2.34 μM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

Figure optionsDownload as PowerPoint slide