刘坚教授、康振辉教授及其合作者在Sci. Adv.上发表论文

High-throughput glycolytic inhibitor discovery targeting glioblastoma by graphite dots–assisted LDI mass spectrometry

作者：

Rui Shi^1†, Peichen Pan^2,3,4†, Rui Lv^1†, Chongqing Ma¹, Enhui Wu¹, Ruochen Guo¹, Zhihao Zhao¹, Hexing Song⁵, Joe Zhou⁵, Yang Liu¹, Guoqiang Xu⁶, Tingjun Hou^2*, Zhenhui Kang^1,7*, Jian Liu^1*

单位：

¹Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.

²College of Pharmaceutical Sciences and State Key Lab of CAD&CG, Zhejiang University, Hangzhou, Zhejiang 310058, China.

³Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

⁴Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

⁵College of Information and Electrical Engineering, China Agricultural University, Beijing, China.

⁶Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.

⁷Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, Macau SAR 999078, China.

摘要：

Malignant tumors will become vulnerable if their uncontrolled biosynthesis and energy consumption engaged in metabolic reprogramming can be cut off. Here, we report finding a glycolytic inhibitor targeting glioblastoma with graphite dots–assisted laser desorption/ionization mass spectrometry as an integrated drug screening and pharmacokinetic platform (GLMSD). We have performed high-throughput virtual screening to narrow an initial library of 240,000 compounds down to the docking of 40 compounds and identified five previously unknown chemical scaffolds as promising hexokinase-2 inhibitors. The best inhibitor (Compd 27) can regulate the reprogrammed metabolic pathway in U87 glioma cells (median inhibitory concentration ~ 11.3 µM) for tumor suppression. Highly effective therapy against glioblastoma has been demonstrated in both subcutaneous and orthotopic brain tumors by synergizing Compd 27 and temozolomide. Our glycolytic inhibitor discovery can inspire personalized medicine targeting reprogrammed metabolisms of malignant tumors. GLMSD enables large, high-quality data for next-generation artificial intelligence–aided drug development.

影响因子：

14.143

分区情况：

一区

链接：

https://www.science.org/doi/10.1126/sciadv.abl4923