基本信息
赵玉军  男  硕导  中国科学院上海药物研究所
电子邮件: yjzhao@simm.ac.cn
通信地址: 上海市浦东新区祖冲之路555号
邮政编码: 201203

研究领域

课题组主要的研究方向是基于药物靶点,开发新颖的小分子化合物分子探针。研究分子探针的分子、细胞、和动物体内活性,探索其中优选的、具有高活性和类药性化合物的成药性,积极推进具有开发潜力药物的临床研究。

主要的研究领域是肿瘤和代谢性疾病。

1.      NIK激酶抑制剂对于肝脏损伤的保护作用研究

    NFκB信号通路包括经典NFκB1信号通路和非经典NFκB2信号通路。经典NFκB1信号通路由p50RelA(RelC)二聚,进而能够启动基因转录;非经典NFκB2信号通路由p52RelB二聚,进而能够启动基因转录。活化的NIK激酶可以促进p100降解生成为p52,进而激活NFκB2信号通路的基因转录。在肝硬化病人肝组织内,NIK mRNA水平升高;毒素和氧化应激也能够使得小鼠肝脏中NIK mRNA水平升高。NIK高表达会诱使肝细胞分泌炎症因子,造成炎症和组织坏死,从而导致小鼠死亡。我们的研究发现,利用小分子NIK激酶抑制剂,可以显著降低p52的蛋白水平,进而抑制NFκB2信号通路。在小鼠模型内,NIK激酶抑制剂B022可以抑制NFκB2信号通路,进而抑制炎症因子THFαIL-6CCL2CCL5, CXCL5和氧化应激因子iNOS mRNA生成,显著减轻了毒素诱导的肝脏细胞调亡,延长了肝损伤小鼠的生存时间。我们的研究表明,NIK抑制剂具有治疗肝损伤的潜在药用价值。

2.      BET Bromodomain抑制剂的抗肿瘤活性研究

BET家族蛋白的Bromodomain结构域可以识别乙酰化赖氨酸,家族蛋白中的BRD4是连接组蛋白和RNA聚合酶II 的关键桥梁。最近的医学、生物学、药学研究成果表明,抑制BET Bromodomain的小分子化合物,可能被用于治疗BET Bromodomain调控异常引起的癌症、炎症、心脏功能衰竭和其他特定疾病,国际上相关的临床研究已经进行到二期阶段。我们开发了一类新颖的、具有较高选择性BET Bromodomain小分子抑制剂,在部分三阴性乳腺癌细胞内具有良好抗肿瘤活性。通过联合用药的方式,我们在具有原发性耐药的肿瘤细胞株内,提高了BET Bromodomain抑制剂的抗肿瘤活性。目前,这一类化合物的成药性深入研究正在进行之中。


招生信息

招收药物化学专业硕士生,博士生和对药物化学研究感兴趣、具有较好小分子合成功底的博士后


招生专业
100701-药物化学
招生方向
抗癌药物,神经药物研究
糖尿病药物,抗菌药物研究
药物合成

教育背景

2005-05--2009-01   新加坡南洋理工大学   博士
2003-08--2005-04   新加坡国立大学   博士肄业
1999-09--2003-06   苏州大学   学士

教授课程

   
Module 1
Advance Organic Synthesis for International Students

指导学生

现指导学生

陈德恒  02  67128  

李志强   02  67128  

论文

1.        Xiaomeng Ren, Xinzhi Li, Linna Jia, Deheng Chen, Hai Hou, Liangyou Rui, Yujun Zhao*, Zheng Chen*, A small-molecule inhibitor of NF-kB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury, FASEB Journal. 2017, 2, 711-718.

2.        Yujun Zhao, Longchuan Bai, Liu Liu, Donna McEachern, Jeanne A. Stuckey, Jennifer L. Meagher, Chao-Yie Yang, Xu Ran, Bing Zhou, Yang Hu, Xiaoqin Li, Bo Wen, Ting Zhao, Siwei Li, Duxin Sun, and Shaomeng Wang*, Structure-Based Discovery of 4-(6-Methoxy-2-methyl-4-(quinolin-4-yl)-9H- pyrimido [4,5-b]indol-7-yl)-3,5-dimethylisoxazole (CD161) as a Potent and Orally Bioavailable BET Bromodomain Inhibitor, Journal of Medicinal Chemistry2017, 60 (9), 3887–3901.

3.        Shaomeng Wang*, Yujun Zhao, Angelo Aguilar, Denzil Bernard, and Chao-Yie Yang, Targeting the MDM2–p53 Protein–Protein Interaction for New Cancer Therapy: Progress and Challenges, Cold Spring Harb Perspect Med, 2017, doi: 10.1101/cshperspect.a026245

4.        Longchuan Bai, Bing Zhou, Chao-Yie Yang, Jiao Ji, Donna McEachern, Sally Przybranowski, Hui Jiang, Jiantao Hu, Fuming Xu, Yujun Zhao, Liu Liu, Ester Fernandez-Salas, Jing Xu, Yali Dou, Bo Wen, Duxin Sun, Jennifer Meagher, Jeanne Stuckey, Daniel F. Hayes, Shunqiang Li, Matthew J. Ellis, Shaomeng Wang*, Targeted degradation of BET proteins in triple-negative breast cancer, Cancer Research, 2017, 77 (9) 2476-2487.

5.        Bing Zhou, Jiantao Hu, Fuming Xu, Zhuo Chen, Longchuan Bai, Ester Fernandez-Salas, Mei Lin, Liu Liu, Chao-Yie Yang, Yujun Zhao, Donna McEachern, Sally Przybranowski, Bo Wen, Duxin Sun, and Shaomeng Wang*, Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression, Journal of Medicinal Chemistry2017, DOI: 10.1021/acs.jmedchem.6b01816.

6.        Xu Ran, Yujun Zhao, Liu Liu, Longchuan Bai, Chao-Yie Yang, Bing Zhou, Jennifer L. Meagher, Krishnapriya Chinnaswamy, Jeanne A. Stuckey, and Shaomeng Wang*, Structure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors, Journal of Medicinal Chemistry, 2015, 58 (12), 4927-4939.

7.        C. Gianna Hoffman-Luca, Daniel Ziazadeh, Donna McEachern, Yujun Zhao, Wei Sun, Laurent Debussche and Shaomeng Wang*, Elucidation of Acquired Resistance to Bcl-2 and MDM2 Inhibitors in Acute Leukemia in Vitro and in Vivo, Clinical Cancer Research, 2015, 21(11), 2558-2568.

8.        Yujun Zhao, Angelo Aguilar, Denzil Bernard, Shaomeng Wang*, Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment, Journal of Medicinal Chemistry, 2015, 58 (3), 1038-1052. 

9.        Shaomeng Wang, Wei Sun, Yujun Zhao, Donna McEachern, Isabelle Meaux, Cédric Barrière, Jeanne A. Stuckey, Jennifer L. Meagher, Longchuan Bai, Liu Liu, Cassandra Gianna Hoffman-Luca, Jianfeng Lu, Sanjeev Shangary, Shanghai Yu, Denzil Bernard, Angelo Aguilar, Odette Dos-Santos, Laurent Besret, Stéphane Guerif, Pascal Pannier, Dimitri Gorge-Bernat, and Laurent Debussche, SAR405838: An Optimized MDM2-p53 Interaction Inhibitor in Clinical Development Inducing Complete and Durable Tumor Regression, Cancer Research, 2014, 74, 5855-5865.

10.    Yujun Zhao, Liu Liu, Wei Sun, Jianfeng Lu, Donna McEachern, Xiaoqin Li, Shanghai Yu, Denzil Bernard, Philippe Ochsenbein, Vincent Ferey, Jean-Christophe Carry, Jeffrey R. Deschamps, Duxin Sun, Shaomeng Wang*, Diastereomeric Spirooxindoles as Highly Potent and Efficacious MDM2 Inhibitors, Journal of the American Chemical Society, 2013, 135, 7223–7234.

11.    Yujun Zhao, Shanghai Yu, Wei Sun, Liu Liu, Jianfeng Lu, Donna McEachern, Sanjeev Shargary, Denzil Bernard, Xiaoqin Li, Ting Zhao, Peng Zou, Duxin Su, Shaomeng Wang*, A Potent Small-Molecule Inhibitor of the MDM2-p53 Interaction (MI-888) Achieved Complete and Durable Tumor Regression in Mice, Journal of Medicinal Chemistry, 2013, 56, 5553-5561.

12.    Yujun Zhao*, Chao-Yie Yang, Shaomeng Wang*, The Making of I-BET762, a BET Bromodomain Inhibitor Now in Clinical Development, Journal of Medicinal Chemistry, 2013, 56, 7498–7500.

13.    Yujun Zhao, Denzil Bernard, Shaomeng Wang*, Small Molecule Inhibitors of MDM2-p53 and MDMX-p53 Interactions as New Cancer Therapeutics, BioDiscovery, 2013, 8: 4, 1-15.

14.    Bin Li, Yujun Zhao, Yin-Chang Lai, Teck-Peng Loh*, Asymmetric Syntheses of 8-Oxabicyclo[3,2,1]octanes: A Cationic Cascade Cyclization, Angewandte Chemie International Edition, 2012, 51, 8041–8045.

15.    Denzil Bernard, Yujun Zhao, Shaomeng Wang*, AM-8553: A Novel MDM2 Inhibitor with a Promising Outlook for Potential Clinical Development, Journal of Medicinal Chemistry, 2012, 55, 4934–4935.

16.    Bin Li, Yin-Chang Lai, Yujun Zhao, Yiu-Hang Wang, Zhi-Liang Shen, Teck-Peng Loh*, Synthesis of 3-Oxaterpenoids and Its Application in the Total Synthesis of (±)-Moluccanic Acid Methyl Ester, Angewandte Chemie International Edition, 2012, 51, 10619–10623.

17.    Zheng Chen, Liang Sheng, Hong Shen, Yujun Zhao, Shaomeng Wang, Robert Brink, Liangyou Rui*, Hepatic TRAF2 Regulates Glucose Metabolism Through Enhancing Glucagon Responses, Diabetes, 2012, 61(3), 566–573.

18.    Yujun Zhao, Bin Li, Li-Jun Serena Tan, Zhi-Liang Shen, Teck-Peng Loh*, Enantioselective Cationic Polyene Cyclization vs Enantioselective Intramolecular Carbonyl–Ene Reaction, Journal of the American Chemical Society, 2010, 132, 10242–10244.

19.    Yujun Zhao, Serena, Li-Jun Tan, Bin Li,  Si-Min Li and Teck-Peng Loh*, Bio-inspired Polyene Cyclization: Aziridinyl Polyene Cyclization Catalyzed by InBr3. Chemical Communication (UK), 2009, 3738–3740.

20.    Yujun Zhao, Teck-Peng Loh*, Asymmetric Total Synthesis of Antiochic Acid, Organic Letters, 2008, 10, 21432145.

21.    Yujun Zhao, Teck-Peng Loh*, Bio-inspired Polyene Cyclization: Synthesis of Tetracyclic Terpenoids Promoted by Steroidal Acetal-SnCl4, Chemical Communication (UK), 2008, 1434–1436.

22.    Yujun Zhao, Teck-Peng Loh*, Practical Synthesis of 1,5-Dimethyl Substituted Conjugated Polyenes from Geranyl Acetate, Tetrahedron, 2008, 64, 49724978.

23.    Jun-Feng Zhao, Yujun Zhao, Teck-Peng Loh, Indium Tribromide-promoted Arene Terminated Epoxy Olefin Cyclization, Chemical Communication (UK), 2008, 1353–1355.

24.    Yujun Zhao, Teck-Peng Loh, Bio-inspired Polyene Cyclization Promoted by Intermolecular Acetal-SnCl4 or N-Acetal-TiCl4: Investigation of the Mechanism and Identification of the Key Intermediates. Journal of the American Chemical Society, 2008, 130, 10024–10029.

25.    Yujun Zhao, Shu-Sin Chng, Teck-Peng Loh, Lewis Acid-Promoted Intermolecular Acetal-Initiated Cationic Polyene Cyclizations. Journal of the American Chemical Society, 2007, 129, 492–493.


专利

国际专利

1. Shaomeng Wang*; Yujun Zhao; Bing Zhou; Angelo Aguilar, Liu Liu, Longchuan Bai, Donna McEachern, Duxin Sun, Bo Wen, Ruijuan Luo, and Ting Zhao, 9H-Pyrimido[4,5-B]indoles and Related Analogs as BET Bromodomain Inhibitors, 2015.2, US Patent No.: US9580430 B2

2. Shaomeng Wang*; Xu Ran; Yujun Zhao; Chao-Yie Yang; Liu Liu; Longchuan Bai; Donna McEachern; Jeanne Stuckey; Jennifer Lynn Meagher; Duxin Sun; Xiaoqin Li; Bing Zhou; Hacer Karatas; Ruijuan Luo; Arul Chinnaiyan; Irfan A. Asangani; BET Bromodomain Inhibitors and therapeutic Methods Using the same, 2014.10.9, PCT Patent Publication No.: 2014/164596 A1

3. Shaomeng Wang*; Yujun Zhao; Wei Sun; Sanjeev Kumar; Lance Leopold; Laurent Debussche; Cedric Barriere; Jeanchristophe Carry; Kwame Amaning, Spiro-Oxindole MDM2 Antagonists, 2012.5.18, PCT Patent Publication No.: WO 2012/065022 A2; US Patent Publication No.: US 2012/0122947; China Patent Publication No.: CN103298818A; European Patent Publication No.: EP2638046 A4

4. Shaomeng Wang*; Shanghai Yu; Wei Sun; Sanjeev Kumar Shangary; Duxin, Sun; Peng Zou; Donna McEachern; Yujun Zhao, Spiro-Oxindole MDM2 Antagonists, 2011.5.19, US Patent No.: US8518984 B2 (2013.8.27); PCT Patent Publication No.: WO 2011/060049; China Patent Publication No.: CN102712650 A; European Patent Publication No.: EP2499145 A2

5. Shaomeng Wang*; Jianyong Chen, Yujun Zhao, Cindy Gomez, Longchuan Bai, Zeneta Nikolovska-Coleska, STAT3 Ligands and Therapeutic Uses Thereof, 2010.7.8, PCT Patent Publication No.: WO 2010/077589; US Patent Publication No.: US 2011/0319362; China Patent Publication No.: CN 200980156486; European Patent Publication No.: EP2373658 A4

6. Teck-Peng Loh*, Yujun Zhao, Cyclization Process of Forming a Multiple Ring Compound. 2007.2, US Patent No.: US8227645 B2 (2012.1.4); PCT Patent Publication No.: WO 2007/097719.


中国专利:

1. 赵玉军、陈德恒、郭德祥、严子琴、周飞龙、耿美玉、丁健、沈爱军、刘红椿、张敏敏,一种BRD4 抑制剂及其制备和应用,中国专利申请号: 201710240864.4, 申请日期: 2017-04-13;

2. 赵玉军、郭德祥、严子琴,含有共轭联烯酰胺结构的化合物、其制备方法、药物组合物和用途, 中国专利申请号: 201611007610.X, 申请日期: 2016-11-16;

3. 赵玉军、陈德恒、严子琴,含有共轭联烯结构的化合物、其药物组合物和用途, 中国专利申请号: 201610679711.5, 申请日期: 2016-08-18.