Structure-based virtual screening towards the discovery of novel FOXM1 inhibitors

Abstract

Aim: Given the importance of FOXM1 in the treatment of ovarian cancer, we aimed to identify an excellent specific inhibitor and examined its underlying therapeutic effect. Materials & methods: The binding statistics for FDI-6 with FOXM1 were calculated through computer-aided drug design. We selected XST-119 through virtual screening, performed surface plasmon resonance and in vitro cell antiproliferative activity analysis and evaluated its antitumor efficacy in a mouse model. Results: XST-119 had significantly higher affinity for FOXM1 and antiproliferative activity than FDI-6. XST-119 had a definite inhibitory activity in a xenograft mouse model. Conclusion: We identified XST-119, a FOXM1 inhibitor, with better efficacy for treatment of ovarian cancer. FOXM1 binding sites for small molecules are also highlighted, which may provide the foundation for further drug discovery.