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研究队伍
姓 名:
 赵玉军
性 别:
 男
职 称:
 研究员
学 历:
 博士
电 话:
 
传 真:
 
电子邮件:
 yjzhao@simm.ac.cn
个人主页:
通讯地址:
 上海市浦东蔡伦路781号13楼 201203
简历:

教育经历
1999.9–2003.6 苏州大学,化学师范,学士
2003.8–2005.5 新加坡国立大学,有机化学,博士肄业
2005.6–2009.1 新加坡南洋理工大学,有机化学,博士

工作经历
2008.6–2009.5 新加坡南洋理工大学,Research Officer
2009.6–2015.3 美国密西根大学癌症中心,博士后
2015.3–今 中国科学院上海药物科学研究所,研究员


研究方向:
1. 蛋白之间相互作用的小分子抑制剂研究;
2. 靶向药物理性设计合成及在肿瘤治疗中的应用;
3. 新化学合成方法研究;
4. 生物分子探针设计研究。

专家类别:
研究员;青年千人

职务:
研究组长

科研成果:

  1.小分子MDM2抑制剂:首次发现了含有螺环氧化吲哚结构的MDM2抑制剂可以发生手性异构互变。通过这样的手性异构互变,得到了一类更加稳定的MDM2抑制剂,如MI-888和临床药物SAR405838。螺环氧化吲哚MDM2抑制剂专利已经被成功转让给法国制药公司赛诺菲(Sanofi S.A.),创造最高可达3.98亿美元的技术转让预期收益。2012年,SAR405838已经同时在美国和欧洲开始了癌症治疗的一期临床试验 (ClinicalTrials.gov Identifier: NCT01636479 and NCT01985191)。

  2.小分子BET Bromodomain抑制剂:参与研制了一类新颖的小分子BET Bromodomain的抑制剂。最新的生物学研究成果表明,抑制BET Bromodomain的小分子化合物,可以治疗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。我们设计合成的BET Bromodomain小分子抑制剂,与BET Bromodomain蛋白集合率Ki < 1 nM,对肿瘤细胞株生长抑制IC50 ≤ 10 nM。在多个SCID小鼠移植瘤模型中,口服给药之后, 表现出优异抗癌疗效。2014年,关于Bromodomain抑制剂两项专利已经成功转让给美国Medivation公司。

  3.小分子STAT3抑制剂:参与研制了基于gp130多肽片段一类拟肽化合物,它们与STAT3蛋白的结合力常数最强达到Ki = 2 nM。转录因子STAT3蛋白的过度表达及伴随的磷酸化和STAT3蛋白二聚,对许多癌症形成和生长起到重要作用。因此,研究STAT3磷酸化及二聚的小分子抑制剂具有潜在的抗癌前景。在STAT3过度表达乳腺癌和前列腺癌细胞内,我们研制的拟肽化合物显著抑制了STAT3磷酸化。同时,化合物表现出对于其他STAT家族蛋白的优异选择性。

  4.仿生多烯环化反应( Biomimetic Polyene Cyclization): 利用手性的缩醛或者手性的1,3-噁唑呤作为手型辅剂, 以SnCl4 或者 TiCl4作为Lewis酸引发不对称仿生多烯环化反应,产物选择性好产率高, 可合成多样化的类萜类化合物。在催化量的InBr3作用下,利用手性环乙胺,引发仿生多烯环化反应,产物选择性好产率高。利用Pybox-Sc(OTf)3催化α-羰基酯引发手性仿生多烯环化反应, 产物选择性好产率高, 可用来合成重要的药物中间体。


承担科研项目情况:

社会任职:

获奖及荣誉:
入选2015年中组部“青年千人”计划

代表论著:

  1.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, DOI: 10.1158/1078-0432.CCR-14-2506

  2.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.

  3.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.

  4.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.

  5.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.

  6.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.

  7.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.

  8.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.

  9.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.

  10.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.

  11.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.

  12.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.

  13.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.

  14.Yujun Zhao, Teck-Peng Loh*, Asymmetric Total Synthesis of Antiochic Acid, Organic Letters, 2008, 10, 2143–2145.

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

  16.Yujun Zhao, Teck-Peng Loh*, Practical Synthesis of 1,5-Dimethyl Substituted Conjugated Polyenes from Geranyl Acetate, Tetrahedron, 2008, 64, 4972–4978.

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

  18.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.

  19.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.

学术专著:

  Shaomeng Wang*, Yujun Zhao, Denzil Bernard, Angelo Aguilar, Sanjeev Kumar, Protein-Protein Interactions (Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics), Springer-Verlag Berlin Heidelberg , 2012, Vol. 8, 57-80,

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 Application Number: 61/950,406

  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, PCT Publication Number: 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, PCT Publication Number: WO 2012/065022 A2; US Patent Publication Number: US 2012/0122947; Chinese Patent Publication Number: CN103298818A; European Patent Publication Number: EP2638046 A4

  4. Shaomeng Wang*; Shanghai Yu; Wei Sun; Sanjeev Kumar Shangary; Duxin, Sun; Peng Zou; Donna McEachern; Yujun Zhao, Spiro-Oxindole MDM2 Antagonists, 2011.10, US Patent Number: US8518984 B2; PCT Publication Number: WO 2011/060049; Chinese Patent Publication Number: CN102712650 A; European Patent Publication Number: EP2499145 A2

  5. Shaomeng Wang*; Jianyong Chen, Yujun Zhao, Cindy Gomez, Longchuan Bai, Zeneta Nikolovska-Coleska, STAT3 Ligands and Therapeutic Uses Thereof, 2010.7, PCT Publication Number: WO 2010/077589; US Patent Publication Number: US 2011/0319362; Chinese Patent Publication Number: CN 200980156486; European Patent Publication Number: EP2373658 A4

  6. Teck-Peng Loh*, Yujun Zhao, Cyclization Process of Forming a Multiple Ring Compound. 2007.2, US Patent Number: US8227645 B2; PCT Publication Number: WO 2007/097719.