Small molecule targeting FOXM1 DNA binding domain exhibits anti-tumor activity in ovarian cancer.

FOXM1 is a potent oncogenic transcription factor essential for cancer initiation, progression, and drug resistance. FOXM1 regulatory network is a major predictor of adverse outcomes in various human cancers. Inhibition of FOXM1 transcription factor function is a potential strategy in cancer treatment. In this study, we performed structure-based in silico screening to discover small molecules targeting the FOXM1 DNA-binding domain (DBD). Compound XST-20 was identified to effectively suppress FOXM1 transcriptional activities and inhibit ovarian cancer cell proliferation. XST-20 directly interacts with the FOXM1 DNA-binding domain determined by SPR assay. Furthermore, XST-20 was found to significantly reduce the colony-forming efficiency and induce cell cycle arrest and apoptosis. Our study provides a lead compound of FOXM1 inhibitor which may serve as a potential targeted therapy agent for ovarian cancer.