癌症干细胞(CSC)是很多癌症复发和转移的根源。靶向CSC有望给癌症治疗带来革命性的进步。但是, 很难发现抗CSC的化合物, 相关天然产物也极少, 且成药性差，靶点不明确或者未知。申请人完成了小白菊内酯、Rakicidin等抗CSC天然产物的首次全合成, 确定了其多个未知的手性中心, 从而获得多个系列的类似物库, 显著提高其活性、稳定性，以及抗CSC的选择性。其中的候选药物ACT001，安全性高，对脑胶质瘤的疗效显著，已获澳大利亚临床试验许可，这种进入发达国家临床试验的“first class”新药, 在我国实属罕见。申请人近年来发表SCI论文20篇, 其中包含1篇JACS，4篇JMC, 在研究方向与分子结构等方面，均具有很强的原创性，为探索抗CSC的靶点奠定了基础， 并有望为恶性胶质瘤这一世界性难题提供新的治疗药物。申请人开辟了抗CSC药物研究新领域，将对抗癌药物的研发策略产生重要影响。

Cancer stem cells (CSC) play key role in the relapse and metastasis of many types of cancers. Targeting CSC may revolutionize the cancer therapy. However, it is very difficult to discover anti-CSC compound, and such natural products with anti-CSC properties are very rare, and Cancer stem cells (CSC) play key role in the relapse and metastasis of many types of cancers. Targeting CSC may revolutionize the cancer therapy. However, it is very difficult to discover anti-CSC compound, and such natural products with anti-CSC properties are very rare, and have serious drugability problem. We complete the first total syntheses of several anti-CSC natural products, and confirm the absolute configuration of their unknown chiral centers, and then obtain several series of analogs, with significantly improved activities, stabilities, and selectivity against CSC. and provide opportunity to explore the target of CSC. We also discovered the drug candidate ACT001, which demonstrate excellent safety profile, and high efficacy against GBM, and ACT001 have been accepted into the clinical trial in Australia, it is one of the rare drug candidates to enter the clinical trial in developed countries. The patent of the new structure of ACT001 have been authorized in China, USA and Europe, and so on. Over 20 SCI papers have been published, including 1 article in JACS, 4 articles in JMC. The research demonstrate high novelty in research area, molecular structure, target exploration, and provide potential drug for the therapy of glioma. The applicant have established a new research area of anti-CSC, and these work will have significant impact to the research strategy of anti-cancer drug.