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Updated: Oct 12, 2025
Fluorescence-Based Detection of FEN1 Nuclease Activity and Screening of Small-Molecule Inhibitors
Published on: June 27, 2025
Structure-based virtual screening towards the discovery of novel FOXM1 inhibitors
Zhuo-Song Xie1, Zi-Ying Zhou1, Lian-Qi Sun1
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
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.
Insights
Researchers identified XST-119, a potent Forkhead box protein M1 (FOXM1) inhibitor, demonstrating superior efficacy in preclinical ovarian cancer models. This discovery offers a promising new therapeutic strategy for ovarian cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Forkhead box protein M1 (FOXM1) is crucial in ovarian cancer progression.
- Targeting FOXM1 presents a potential therapeutic strategy for ovarian cancer.
- Developing specific and effective FOXM1 inhibitors is a key research objective.
Purpose of the Study:
- To identify a potent and specific inhibitor of FOXM1.
- To evaluate the therapeutic efficacy of the identified inhibitor in ovarian cancer models.
- To understand the binding interactions of small molecules with FOXM1.
Main Methods:
- Computer-aided drug design was used to calculate binding statistics for FDI-6 with FOXM1.
- Virtual screening identified XST-119 as a potential candidate.
- Surface plasmon resonance, in vitro antiproliferative assays, and xenograft mouse models were employed for evaluation.
Main Results:
- XST-119 exhibited significantly higher affinity for FOXM1 compared to FDI-6.
- XST-119 demonstrated potent antiproliferative activity against ovarian cancer cells.
- XST-119 showed significant antitumor efficacy in a xenograft mouse model.
Conclusions:
- XST-119 is a highly effective FOXM1 inhibitor for ovarian cancer treatment.
- The study highlights FOXM1 binding sites, aiding future drug discovery efforts.
- XST-119 represents a promising therapeutic candidate for ovarian cancer.
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