胶质瘤是最常见和最致命的脑肿瘤，临床迫切需要抗胶质瘤新药物。肿瘤细胞特征性代谢为胶质瘤的治疗提供了新靶标。目前靶向肿瘤代谢某单一靶标或信号通路的小分子抗肿瘤药的研究未取得期待的突破。前期研究发现，数个天然小分子干预肿瘤不同代谢途径的特异关键酶、生物小分子和癌基因，具有抗胶质瘤活性强和毒性低的特点，提示多靶标调控肿瘤代谢研究发现抗胶质瘤活性物质的研究意义和应用前景。本项目以胶质瘤细胞代谢所偏爱依赖的数个特异关键酶、生物小分子和癌基因为靶标，构建多靶标研究发现抗胶质瘤活性物质的新方法，从前期研究已获得的海洋放线菌(影响肿瘤代谢的活性物质的产生菌)中发现新的抗胶质瘤活性物质，深入研究代表性活性化合物(包括前期研究已获得的四个)的抗胶质瘤生物活性，阐述该研究方法的科学性和应用价值。本项目将为肿瘤代谢多靶标抗胶质瘤活性物质的研究开辟新途径，为新型抗胶质瘤药物的研究提供先导化合物甚至候选药物。

Gliomas remain the most common and lethal brain tumors. Therefore, there is an urgent clinical need to discover and develop novel anti-glioma drugs. Tumor cell metabolic reprogramming provides new targets for gliomas therapy. The discovery and development of small molecular antitumor agents through the manipulation of single molecular target or pathway of tumor metabolism have not made anticipated breakthroughs so far. Our preliminary studies indicated that the regulation of multiple glioma metabolic enzymes, biological small molecules, and oncogenes by several natural compounds produced potent anti-glioma activity with low toxicity, suggesting the scientific significance and application prospect of the modulation of multiple targets of tumor metabolism for the discovery of novel anti-glioma agents. This proposal has three specific aims. Aim I: To develop a new method by targeting several metabolic regulators of key enzymes, biological small molecules, and oncogenes, which are related to the tumorigenesis of gliomas, for the discovery and study of anti-glioma agents. Aim II: To discover novel anti-glioma compounds from cultures of marine microorganisms obtained from the prophase study, which produced anti-glioma metabolites targeting the tumor metabolism. Aim III: To intensively investigate the anti-glioma effects and mechanisms of action of the representative anti-glioma compounds, including four novel ones from marine actinomycetes in our previous investigation for this study. This study will open a new window for the discovery and study of novel anti-glioma agents by targeting multiple regulators of tumor metabolism and provide lead compounds, even candidate drugs, for the development of novel anti-glioma drugs.