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Updated: Oct 3, 2025
Glycomics-Guided Glycoproteomics Facilitates Comprehensive Profiling of the Glycoproteome in Complex Tumor Microenvironments
Published on: February 7, 2025
High-throughput glycolytic inhibitor discovery targeting glioblastoma by graphite dots-assisted LDI mass spectrometry
Rui Shi1, Peichen Pan2,3,4, Rui Lv1
1Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Abstract:
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.
Insights
Researchers discovered a new glycolytic inhibitor targeting glioblastoma, a type of brain cancer. This novel compound, Compd 27, effectively suppresses tumor growth and shows promise for personalized medicine approaches in cancer treatment.
Area of Science:
- Oncology
- Biochemistry
- Drug Discovery
Background:
- Malignant tumors exhibit metabolic reprogramming, enhancing uncontrolled biosynthesis and energy consumption.
- Targeting these altered metabolic pathways offers a potential strategy for cancer therapy.
Purpose of the Study:
- To identify novel glycolytic inhibitors for glioblastoma treatment.
- To develop an integrated platform for drug screening and pharmacokinetic analysis.
Main Methods:
- High-throughput virtual screening of 240,000 compounds.
- Utilized graphite dots-assisted laser desorption/ionization mass spectrometry (GLMSD) for drug screening.
- Evaluated inhibitor efficacy in U87 glioma cells and in vivo glioblastoma models.
Main Results:
- Identified five novel chemical scaffolds as potent hexokinase-2 inhibitors.
- Compound 27 demonstrated significant glioblastoma suppression in vitro and in vivo.
- Synergistic therapeutic effect observed when combining Compound 27 with temozolomide.
Conclusions:
- Discovery of a promising glycolytic inhibitor for glioblastoma.
- GLMSD platform facilitates efficient drug discovery and development.
- Findings support personalized medicine strategies targeting tumor metabolism.
