1.Medicinal Chemistry of Anti-Cancer Stem Cells

2. Target Identification of Complex Natural Products and Its Medicical Chemsitry

Many studies suggested that cancer stem cells play a key role in the cancer initiation, development, relapse and drug resistance. Therefore, calling for more anti-CSC compounds and study of their possible target are highly concerned. Unfortunately, small molecules that can selectively ablate cancer stem cells (CSCs) are very rare. We completed the first total synthesis of a series of terpene lactones (including partholide and ovatodiolide) and APD-cyclic depsipeptides (including rakicidin A and BE-43547A2) that can selectively eradicate cancer stem cell. We also conducted the medicinal chemistry study of these compounds. We built the compounds library targeting CSC. One of the compounds ACT001, which demostrated excellent safety profile and high efficacy against GBM has completed the Phase I clinical trail within the preset dose in Australia. Part of the Clinical I data has been indexed in J. Clinical Oncology (IF=32). Based on the clinical data, ACT001 has been designated as“orphan drug”by FDA and EMA.

 1990-1994 Hunan Normal University，B.S., P. R. China;

1994.9-1997.7: Shanghai Institute of Organic Chemistry, Chinese Academy of Science, M. S., P. R. China;

1998.9-2003.6: University of Notre Dame, Ph. D., USA;

2003.7-2007.12: Scientist I, II and Project Leader at Kosan Biosciences, California, USA;

2008.1- 2020.10: Prof. at College of Pharmacy， Nankai University, Tianjin, P. R. China.

2020.10-Present: Prof. at College of Chemistry， Nankai University, Tianjin, P. R. China.

1.Junhong Xiang, Yahui Ding,* Jiaxin Li, Xiuhe Zhao, Yuanjun Sun, Da Wang, Liang Wang,* Yue Chen*. Ovatodiolides: Scalable Protection-free Syntheses, Configuration Determination and Biological Evaluation against Hepatic Cancer Stem Cells. Angew. Chem. Int. Ed. 2019, 58, 10587-10590.

2. Jing Li, Shanshan Li, Jianshuang Guo, Qiuying Li, Jing Long, Cheng Ma, Yahui Ding, Chunli Yan, Liangwei Li, Zhigang Wu, He Zhu, Keqin Li, Liuqing Wen, Quan Zhang, Qingqing Xue, Caili Zhao, Ning Liu, Ivaylo Ivanov, Ming Luo, Rimo Xi, Haibo Long, *********,* Yue Chen*. Natural Product Micheliolide (MCL) Irreversibly Activates Pyruvate Kinase M2 and Suppresses Leukemia. J. Med. Chem. 2018, 61, 4155-4164.

3. Yuanjun Sun#, Yahui Ding#, Dongmei Li, Ruifei Zhou, Xiuwen Su, Juan Yang, Xiaoqian Guo, Chuanke Chong, Jinghan Wang, Weicheng Zhang, Cuigai Bai, Liang Wang,* Yue Chen*. Cyclic Depsipeptide BE-43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells. Angew. Chem. Int. Ed. 2017, 56, 14627-14631

4. Jinghan Wang, Beijia Kuang, Xiaoqian Guo, Jianwei Liu, Yahui Ding, Jiangnan Li, Shende Jiang, Ying Liu, Fang Bai, Luyuan Li, Quan Zhang, Xiao-Yu Zhu, Bo Xia, Chun-Qi Li, Liang Wang,* Guang Yang,* Yue Chen*. Total Syntheses and Biological Activities of Vinylamycin Analogs. J. Med. Chem. 2017, 60, 1189-1209.

5. Feng Sang,# Yahui Ding,# Jinghan Wang,# Bingxia Sun,# Jianlei Sun,# Yan Geng,# Zhang Zhang, Ke Ding, Ling-Ling Wu, Jian-Wei Liu, Cuigai Bai, Guang Yang,* Quan Zhang,* Lu-Yuan Li,* Yue Chen*. Structure−Activity Relationship Study of Rakicidins: Overcoming Chronic Myeloid Leukemia Resistance to Imatinib with 4‑Methylester-Rakicidin A. J. Med. Chem. 2016, 59, 1184-1196.

6. Yahui Ding, Qingqing Xue, Shuo Liu, Kai Hu, Da Wang, Tianpeng Wang, Ye Li, Hongyu Guo, Xin Hao, Weizhi Ge, Yan Zhang, Ang Li, Jing Li, * Yue Chen, * Quan Zhang*. Identification of Parthenolide Dimers as Activators of Pyruvate Kinase M2 in Xenografts of Glioblastoma Multiforme In Vivo. J. Med. Chem. 2020, 63, 1597-1611.

7. Feng Sang, Dongmei Li, Xiaolong Sun, Xianqiang Cao, Liang Wang, Jianlei Sun, Bingxia Sun, Lingling Wu, Guang Yang, Xiaoqian Chu, Jinghan Wang, Changming Dong, Yan Geng, Hong Jiang, Haibo Long, Sijia Chen, Guiyan Wang, Shuzhong Zhang, Quan Zhang, Yue Chen,* Total Synthesis and Determination of the Absolute Configuration of Rakicidin A. J. Am. Chem. Soc., 2014, 136, 15787-15791.

8. Jing Long, Shan-Feng Zhang, Pan-Pan Wang, Xue-Mei Zhang, Zhong-Jin Yang, Quan Zhang*, Yue Chen,*Total syntheses of parthenolide and its analogs with macrocyclic stereocontrol. J. Med. Chem., 2014, 57, 7098-7112.

9. Zhongjin Yang, Weizhi Ge, Qiuying Li, Yaxin Lu, Jianmiao Gong, Beijia Kuang, Xiaonan Xi, Haiting Wu, Quan Zhang,* Yue Chen*. Syntheses and Biological Evaluation of Costunolide, Parthenolide and Their Fluorinated Analogues. J. Med. Chem. 2015, 58, 7007-7020.

10. Quan Zhang, # Yaxin Lu, # Yahui Ding, # Jiadai Zhai, # Qing Ji, # Weiwei Ma, Ming Yang, Hongxia Fan, Jing Long, Bin Han, Wenpeng Zhang, Chuanjiang Qiu, Xiaoyan Ma, Zhongsheng Tong, Yehui Shi, Yongsheng Jia, Qianqian Shi, Haoliang Zhang, Dongmei Li, Jing Zhang, Jianping Lin, Lu-Yuan Li, Yingdai Gao,* Yue Chen,* Guaianolide Sesquiterpene Lactones, a Source to Discover Agents That Selectively Ablate Acute Myelogenous Leukemia Stem and Progenitor Cells. J. Med. Chem., 2012, 55, 8757−8769.