王平原

发布者:张栋发布时间:2023-04-13浏览次数:10

 

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王平原

博士

教授

博士生导师

科 室:

药物化学

办公电话:

0532-82031636

电子邮箱

wangpingyuan@ouc.edu.cn

联系地址:

山东省青岛市鱼山路5号中国海洋大学胜利楼225 266003

研究方向:

  1. 靶向G蛋白偶联受体(GPCR)抗神经精神疾病新药发现;

  2. 活性海洋天然产物的发现、合成及结构优化

个人简介

 

 

 

 

近年来一直从事神经精神疾病分子靶向新药的创制研究,尤其是针对G蛋白偶联受体(GPCR)及下游的信号通路蛋白为靶点的药物先导物发现研究。在EMBO Mol. Med.、J. Med. Chem.、Eur. J. Med. Chem.、Org. Lett.等药物化学主流期刊发表论文30余篇,申请国际、国内发明专利8项,已授权2项,thioparib系列专利获得了多国授权。2019年获得美国德克萨斯大学颁发的Herin转化研究奖“Herin Translation Research Award”。入选2022年山东省“泰山学者”青年专家。

教育背景

 

 

 

 

2010.09-2016.06

华中师范大学&上海药物所

药物化学

博士

2006.09-2010.06

华中师范大学

化学

学士

 

 

 

 

工作经历

 

 

 

 

2021.08至今

中国海洋大学

教授

 

2016.06-2021.06

美国德克萨斯大学医学分部

博士后

 

 

 

 

 

学术兼职

 

 

 

 

中国药学会高级会员

中国海洋湖沼学会高级会员

Journal of Medicinal Chemistry、European Journal of Medicinal Chemistry等杂志审稿人

承担课程

 

 

 

 

有机化学(本科生课程)

海洋药物学(本科生课程)

研究进展

 

 

 

 

近年来G-蛋白偶联受体52(GPR52)及其下游信号蛋白(环腺苷酸直接活化的交换蛋白1,EPAC1和离子通道蛋白(钠通道1.6NaV1.6)开展了分子靶向抗神经精神疾病药物先导物的设计合成与作用机制研究,形成了以下创新性成果:1)设计合成了可口服、高活性的嘧啶吲哚类特异性GPR52激动剂,验证了GPR52激动剂的体内抗精神分裂药效,系统的临床前评价显示了其良好的成药性和开发前景2)设计合成了成药性高选择性EPAC1激动剂拓展了EPAC1激动剂应用于抗神经精神疾病药物研发的新方向3)以钠离子通道1.6位靶点,设计合成了高活性的小分子拟肽化合物为高效、非成瘾抗神经精神疾病药物开发探索提出了新策略

代表性成果

代表性论文

 

 

 

 

加入海大后的代表性论文

  1. Ling Lv, Mireguli Maimaitiming, Yan Huang, Jichen Yang, Shuxia Chen, Yanfeng Sun, Xuetao Zhang, Xin Li, Changhu Xue, Pingyuan Wang*, Chang-Yun Wang*, and Zhiqing Liu*.Discovery of quinazolin-4(3H)-one derivatives as novel AChE inhibitors with anti-inflammatory activities.Eur. J. Med. Chem.,2023, 254, 115346.

  2. Maimaitiming Mireguli, Ling Lv, Xuetao Zhang, Shuli Xia, Xin Li, Pingyuan Wang*,Zhiqing Liu*,and Chang-Yun Wang*. Semi-Synthesis and Biological Evaluation of 25(R)-26-Acetoxy-3β,5α-Dihydroxycholest-6-One.Mar. Drugs,2023, 21, 191.

  3. Li-Min Wang, Pingyuan Wang, Xiao-Min Chen, Hui Yang, Shan-Shan Song, Zilan Song, Li Jia, Hua-Dong Chen, Xu-Bin Bao, Ne Guo, Xia-Juan Huan, Yong Xi, Yan-Yan Shen, Xin-Ying Yang, Yi Su, Yi-Ming Sun, Ying-Lei Gao, Yi Chen, Jian Ding, Jing-Yu Lang*, Ze-Hong Miao*, Ao Zhang*and Jin-Xue He*. Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance. EMBO Mol. Med., 2023, 15, e16235.

加入海大的代表性论文

  1. Pingyuan Wang, Dharini van der Hoeven, Na Ye, Haiying Chen, Zhiqing Liu, Xiaoping Ma, Dina Montufar-Solis, Kristen M. Rehl, Kwang-Jin Cho, Sabita Thapa, Wei Chen, Ransome van der Hoeven, Jeffrey A. Frost, John F. Hancock* and Jia Zhou*.Scaffold repurposing of fendiline: Identification of potent KRAS plasma membrane localization inhibitorsEur. J. Med. Chem.,2021, 217, 113381.

  2. Zhiqing Liu*, Pingyuan Wang, Eric A Wold, Qiaoling Song, Chenyang Zhao, Changyun Wang* and Jia Zhou*. Small-Molecule Inhibitors Targeting the Canonical WNT Signaling Pathway for the Treatment of Cancer. J. Med. Chem.,2021,64, 4257-4288.

  3. Pingyuan Wang, Paul A Wadsworth, Nolan M Dvorak, Aditya K Singh, Haiying Chen, Zhiqing Liu, Richard Zhou, Luis Marcelo F Holthauzen, Jia Zhou* and Fernanda Laezza*. Design, Synthesis, and Pharmacological Evaluation of Analogues Derived from the PLEV Tetrapeptide as Protein-Protein Interaction Modulators of Voltage-Gated Sodium Channel 1.6. J. Med. Chem.,2020, 63, 11522-11547.

  4. Pingyuan Wang, Urszula Luchowska-Stańska, Boy van Basten, Haiying Chen, Zhiqing Liu, Jolanta Wiejak, Padraic Whelan, David Morgan, Emma Lochhead, Graeme Barker*, Holger Rehmann, Stephen J Yarwood* and Jia Zhou*. Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators.J. Med. Chem.,2020, 63, 5159-5184.

  5. Pingyuan Wang, Daniel E Felsing, Haiying Chen, Sonja J Stutz, Ryan E Murphy, Kathryn A Cunningham, John A Allen* and Jia Zhou*. Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior.J. Med. Chem.,2020, 63, 13951-13972.

  6. Pingyuan Wang, Jia Zhou*. Proteolysis Targeting Chimera (PROTAC): A Paradigm-Shifting Approach in Small Molecule Drug Discovery. Curr. Top. Med. Chem. 2018, 18, 1354-1356.

  7. Zhiqing Liu, Pingyuan Wang, Haiying Chen, Eric A Wold, Bing Tian, Allan R Brasier and Jia Zhou*.Drug Discovery Targeting Bromodomain-Containing Protein 4. J. Med. Chem.,2017, 60, 4533-4558.

  8. Pingyuan Wang, Zhiqing Liu, Haiying Chen, Na Ye, Xiaodong Cheng and Jia Zhou*. xchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets. Bioorg. Med. Chem. Lett.,2017, 27, 1633-1639.

  9. Ying-Qing Wang, Pingyuan Wang, Yu-Ting Wang, Guang-Fu Yang, Ao Zhang* and Ze-Hong Miao*.An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy. J. Med. Chem.,2016, 59, 9575-9598.

  10. Pingyuan Wang, Shanshan Song, Zehong Miao, Guangfu Yang* and Ao Zhang*. InBr3-Mediated One-Pot Synthesis of 2-(Polyhydroxylatedalkyl)-N-aryl-/-alkylpyrroles from 1,2-Cyclopropa-3-pyranone and Amines.Org. Lett.,2013, 15, 3852-3855.

专利

 

 

 

 

  1. Wang, Changyun; Liu, Zhiqing; Yang, Jinbo; Zhao, Chenyang; Wang, Pingyuan; Zhou, Yue; Li, Rui; Zhang, Xinxin; Yang, Lujia. Diketopiperazine marine natural product pretrichodermamide B derivative and its preparation method, and application of pretrichodermamide B and its derivative in antitumor drug capable of inhibiting JAK/STAT3 signaling pathway. Zhuanli Shenqing (2022), ZL202210076797.8.

  2. Zhou, Jia; Allen, John A.; Wang, Pingyuan; Felsing, Daniel E.Heterocyclic compounds used as G-protein-coupled receptor 52 agonists. U.S. Pat. Appl. Publ. (2022), US 20220112164 A1 20220414.

  3. Zhou, Jia; Yarwood, Stephen; Wang, Pingyuan; Luchowska-Stanska, Urszula; Van Basten, Boy. Selective non-cyclic nucleotide activators for the camp sensor EPAC1. From PCT Int. Appl. (2021), WO 2021188728 A1 20210923.

  4. Hancock, John; Zhou, Jia; Van der Hoeven, Dharini; Frost, Jeffery A.; Ye, Na; Wang, Pingyuan. Preparation of fendiline derivatives as KRAS modulators. PCT Int. Appl. (2020), WO 2020181143 A1 20200910.

  5. Laezza, Fernanda; Zhou, Jia; Chung, Jin Mo; Wang, Pingyuan; La, Jun-Ho; Folorunso, Oluwarotimi; Singh, Aditya. Novel non-opioid anti-pain medication. PCT Int. Appl. (2020), WO 2020154679 A1 20200730. 

  6. Zhang, Ao; Miao, Zehong; Wang, Pingyuan; Song, Shanshan; Song, Zilan; Huan, Xiajuan; Fan, Zhoulong; Ding, Jian. Substituted triazolopiperazine PARP inhibitor, preparation method therefor, and use thereof. PCT Int. Appl. (2017), WO 2017088723 A1 20170601.

  7. Zhang, Ao; Miao, Zehong; Wang, Pingyuan; Huan, Xiajuan; Ding, Jian. Substituted triazolopiperazine PARP inhibitor, preparation method therefor, and use thereof. Faming Zhuanli Shenqing (2017), CN 106749261 A 20170531.

  8. Zhang, Ao; Miao, Zehong; Wang, Pingyuan; Huan, Xiajuan; Ding, Jian. Preparation of nitrogen-containing aryl benzothiazole PARP1 inhibitor and their application. Faming Zhuanli Shenqing (2016), CN 105272936 A 20160127.

获奖

 

 

 

 

  1. Herin Translation Research Award    2019

项目课题

  1. 山东省泰山学者青年专家,2022-2024年 主持

  2. 中国海洋大学“青年英才工程”第一层次启动经费,2021-2025,主持