Xie Zhuo-Song, Zhou Zi-Ying, Sun Lian-Qi, Yi Hong, Xue Si-Tu, Li Zhuo-Rong
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Future Med Chem. 2022 Feb;14(4):207-219. doi: 10.4155/fmc-2021-0282. Epub 2021 Nov 23.
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. 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 cell antiproliferative activity analysis and evaluated its antitumor efficacy in a mouse model. 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. 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.
鉴于FOXM1在卵巢癌治疗中的重要性，我们旨在鉴定一种出色的特异性抑制剂，并研究其潜在的治疗效果。通过计算机辅助药物设计计算FDI-6与FOXM1的结合统计数据。我们通过虚拟筛选选择了XST-119，进行了表面等离子体共振和细胞抗增殖活性分析，并在小鼠模型中评估了其抗肿瘤功效。XST-119对FOXM1的亲和力和抗增殖活性明显高于FDI-6。XST-119在异种移植小鼠模型中具有明确的抑制活性。我们鉴定出一种FOXM1抑制剂XST-119，其对卵巢癌的治疗效果更好。还突出显示了小分子的FOXM1结合位点，这可能为进一步的药物发现提供基础。
