小分子靶向药物是临床抗癌药物的重要组成部分。天然先导化合物的发现为新药的候选化合物提供了新颖的分子结构，这是研发抗肿瘤新药的高效途径。因此，以天然产物作为先导化合物进行抗肿瘤药物研发具有巨大的开发潜力和应用前景。本课题组利用高通量筛选技术寻找具有抗癌活性的天然多肽类分子，设计合成具有生物功能的人工多肽分子，研究天然多肽与仿生多肽的抗癌机制，将其应用于肿瘤的靶向治疗。
  主要研究方向包括：1）高通量筛选具有抗肿瘤生物活性的天然多肽；2）寻找和鉴定新的抗肿瘤天然多肽分子靶点；3）通过借鉴和模拟细胞的信号通路和生理过程，设计合成仿生人工多肽分子，应用于抗肿瘤治疗。

    

   

071009-细胞生物学
0703Z1-化学生物学
071010-生物化学与分子生物学

天然产物，多肽分子作用机制，仿生多肽药物
肿瘤靶向治疗

2009-09--2014-06   四川大学 生物治疗国家重点实验室   理学博士
2005-09--2009-07   四川大学 生命科学学院/吴玉章学院   理学学士

化学生物学

（ 1 ） PLK1抑制剂及其制备方法与应用, 发明, 2017, 第 4 作者, 专利号: CN106866635
（ 2 ） 一种Aurora A 蛋白抑制剂及其制备方法和药物用途, 发明, 2019, 第 5 作者, 专利号: CN 109970720

   

[1] Shi, Wenli, Lu, Danyi, Wu, Chunlei, Li, Meiqing, Ding, Zhihao, Li, Yanyan, Chen, Binghua, Lin, Xian, Su, Wu, Shao, Ximing, Xia, Zhihui, Fang, Lijing, Liu, Ke, Li, Hongchang. Coibamide A kills cancer cells through inhibiting autophagy. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS[J]. 2021, 547: 52-58, http://dx.doi.org/10.1016/j.bbrc.2021.01.112.
[2] Wu, Chunlei, Cheng, Zhehong, Lu, Danyi, Liu, Ke, Cheng, Yulian, Wang, Pengxin, Zhou, Yimin, Li, Meiqing, Shao, Ximing, Li, Hongchang, Su, Wu, Fang, Lijing. Novel N-Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy. JOURNAL OF MEDICINAL CHEMISTRY[J]. 2021, 64(2): 991-1000, http://dx.doi.org/10.1021/acs.jmedchem.0c01387.
[3] Tang, Wei, Fang, Fei, Ke, Liu, Huang, Zhi, Li, Hui, Yin, Ying, Wang, Jun, Wang, Guocheng, Wei, Liyu, Ou, Yun, Wang, Yazhou. Aligned Biofunctional Electrospun PLGA-LysoGM1 Scaffold for Traumatic Brain Injury Repair. ACS BIOMATERIALS SCIENCE & ENGINEERING[J]. 2020, 6(4): 2209-2218, [4] Liu, Ke, Zou, Rongfeng, Cui, Wenqiang, Li, Meiqing, Wang, Xueying, Dong, Junlin, Li, Hongchun, Li, Hongpei, Wang, Peihui, Shao, Ximing, Su, Wu, Chan, H C Stephen, Li, Hongchang, Yuan, Shuguang. Clinical HDAC Inhibitors Are Effective Drugs to Prevent the Entry of SARS-CoV2. ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE[J]. 2020, 3(6): 1361-1370, http://dx.doi.org/10.1021/acsptsci.0c00163.
[5] Li, Meiqing, Shao, Ximing, Wu, Chunlei, Lu, Danyi, Liu, Ke, Wang, Wei, Liu, Jiakai, Li, Hongchang, Su, Wu, Fang, Lijing. Chlorotoxin-derived bicyclic peptides for targeted imaging of glioblastomas. CHEMICAL COMMUNICATIONS[J]. 2020, 56(66): 9537-9540, http://dx.doi.org/10.1039/d0cc01089h.
[6] Yao, Guiyang, Wang, Wei, Ao, Lijiao, Cheng, Zhehong, Wu, Chunlei, Pang, Zhengyin, Liu, Ke, Li, Hongchang, Su, Wu, Fang, Lijing. Improved Total Synthesis and Biological Evaluation of Coibamide A Analogues. JOURNAL OF MEDICINAL CHEMISTRY[J]. 2018, 61(19): 8908-8916, http://ir.siat.ac.cn:8080/handle/172644/14615.
[7] Liu, Ke, Fang, Lijing, Sun, Haiyan, Pan, Zhengyin, Zhang, Jianchao, Chen, Juntao, Shao, Ximing, Wang, Wei, Tan, Yuanyan, Ding, Zhihao, Ao, Lijiao, Wu, Chunlei, Liu, Xiaoqi, Li, Huashun, Wang, Rui, Su, Wu, Li, Hongchang. Targeting Polo-like Kinase 1 by a Novel Pyrrole-Imidazole Polyamide-Hoechst Conjugate Suppresses Tumor Growth In Vivo. MOLECULAR CANCER THERAPEUTICS[J]. 2018, 17(5): 988-1002, http://ir.siat.ac.cn:8080/handle/172644/14593.
[8] Ao, Lijiao, Wu, Chunlei, Liu, Ke, Wang, Wei, Fang, Lijing, Huang, Liang, Su, Wu. Polydopamine-Derivated Hierarchical Nanoplatforms for Efficient Dual-Modal Imaging-Guided Combination in Vivo Cancer Therapy. ACS APPLIED MATERIALS & INTERFACES[J]. 2018, 10(15): 12544-12552, http://ir.siat.ac.cn:8080/handle/172644/14592.
[9] Yao, Guiyang, Wang, Wei, Ao, Lijiao, Cheng, Zhehong, Wu, Chunlei, Pang, Zhengyin, Liu, Ke, Li, Hongchang, Su, Wu, Fang, Lijing. Improved Total Synthesis and Biological Evaluation of Coibamide A Analogues. JOURNAL OF MEDICINAL CHEMISTRY[J]. 2018, 61(19): 8908-8916, http://ir.siat.ac.cn:8080/handle/172644/14615.
[10] Pan, Zhengyin, Wu, Chunlei, Wang, Wei, Cheng, Zhehong, Yao, Guiyang, Liu, Ke, Li, Hongchang, Fang, Lijing, Su, Wu. Total Synthesis and Stereochemical Assignment of Gymnopeptides A and B. ORGANIC LETTERS[J]. 2017, 19(17): 4420-4423, https://www.webofscience.com/wos/woscc/full-record/WOS:000409566400003.
[11] Shao, Ximing, Ding, Zhihao, Zhao, Ming, Liu, Ke, Sun, Haiyan, Chen, Juntao, Liu, Xianming, Zhang, Yuzhen, Hong, Yang, Li, Huashun, Li, Hongchang. Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4. JOURNAL OF BIOLOGICAL CHEMISTRY[J]. 2017, 292(50): 20628-20643, http://dx.doi.org/10.1074/jbc.M117.800946.
[12] Sun, Haiyan, Liu, Yi, Zhang, Lei, Shao, Ximing, Liu, Ke, Ding, Zhihao, Liu, Xianming, Jiang, Changan, Li, Huashun, Li, Hongchang. Numb positively regulates autophagic flux via regulating lysosomal function. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS[J]. 2017, 491(3): 780-786, http://dx.doi.org/10.1016/j.bbrc.2017.07.084.
[13] Shao, Ximing, Ding, Zhihao, Zhao, Ming, Liu, Ke, Sun, Haiyan, Chen, Juntao, Liu, Xianming, Zhang, Yuzhen, Hong, Yang, Li, Huashun, Li, Hongchang. Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking of the Notch ligand Delta-like 4. JOURNAL OF BIOLOGICAL CHEMISTRY[J]. 2017, 292(50): 20628-20643, http://dx.doi.org/10.1074/jbc.M117.800946.
[14] Zhang, Jianchao, Shao, Ximing, Sun, Haiyan, Liu, Ke, Ding, Zhihao, Chen, Juntao, Fang, Lijing, Su, Wu, Hong, Yang, Li, Huashun, Li, Hongchang. NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch signaling. ONCOTARGET[J]. 2016, 7(38): 61036-61053, http://dx.doi.org/10.18632/oncotarget.11062.
[15] Liu, Ke, Lei, Run, Li, Qiong, Wang, XinXin, Wu, Qian, An, Peng, Zhang, Jianchao, Zhu, Minyan, Xu, Zhiheng, Hong, Yang, Wang, Fudi, Shen, Ying, Li, Hongchang, Li, Huashun. Transferrin Receptor Controls AMPA Receptor Trafficking Efficiency and Synaptic Plasticity. SCIENTIFIC REPORTS[J]. 2016, 6: https://www.webofscience.com/wos/woscc/full-record/WOS:000370296600001.
[16] Shao, Ximing, Liu, Ke, Fan, Yi, Ding, Zhihao, Chen, Min, Zhu, Minyan, Weinstein, Lee S, Li, Hongchang, Li, Huashun. G alpha(s) Relays Sphingosine-1-Phosphate Receptor 1 Signaling to Stabilize Vascular Endothelial-Cadherin at Endothelial Junctions to Control Mouse Embryonic Vascular Integrity. JOURNAL OF GENETICS AND GENOMICS[J]. 2015, 42(11): 613-624, https://www.webofscience.com/wos/woscc/full-record/WOS:000366136300003.
[17] Liu, Ke, Lin, Quan, Wei, Yanxia, He, Renbing, Shao, Ximing, Ding, Zhihao, Zhang, Jianchao, Zhu, Minyan, Weinstein, Lee S, Hong, Yang, Li, Hongchang, Li, Huashun. G alpha s regulates asymmetric cell division of cortical progenitors by controlling Numb mediated Notch signaling suppression. NEUROSCIENCE LETTERS[J]. 2015, 597: 97-103, https://www.webofscience.com/wos/woscc/full-record/WOS:000356186100018.

   

（ 1 ） 细胞命运决定子Numb调控肿瘤干细胞不对称分裂的分子机制研究, 主持, 国家级, 2018-01--2020-12
（ 2 ） Numb调节乳腺癌干细胞命运的分子机制研究, 主持, 省级, 2017-01--2019-12
（ 3 ） 转铁蛋白受体调控神经系统发育的机制研究, 主持, 部委级, 2015-01--2016-12
（ 4 ） Mon1b协同NSF调控早期内吞体膜融合的机制研究, 参与, 国家级, 2017-01--2020-12
（ 5 ） NUMB通过调控EMT影响三阴性乳腺癌转移的分子机制研究, 参与, 国家级, 2016-01--2018-12
（ 6 ） 细胞形态变化和细胞周期紧密协同的分子机制研究, 参与, 省级, 2018-01--2022-12
（ 7 ） 靶向细胞周期激酶PlK1的抗肿瘤药物研发, 参与, 省级, 2015-01--2017-12
（ 8 ） 纳米分辨X射线微分相衬显微镜, 参与, 国家级, 2021-01--2025-12