• 柳红

    药物化学系 兼职教授
    领域:药物化学基础和应用基础研究
    联系电话:
    电子邮箱:hliu@simm.ac.cn
    办公室:上海市浦东新区祖冲之路555号
    实验室:上海市浦东新区祖冲之路555号
  • 1999年获学院药物化学专业理学博士学位,同年进入中科院上海药物所进行博士后研究,2001年9月博士后出站留所工作至今。现任中国科学院上海药物研究所研究员、博士生导师,新药研究国家重点实验室副主任,中国科学院上海药物研究所学术委员会副主任。主要从事药物化学、药物设计和化学生物学研究。近年来紧扣“新药先导化合物的发现和优化”这条主线,构建了“有机合成新方法促进药物发现”新药研究技术体系,主要针对神经精神系统疾病、代谢性和泌尿系统疾病、病毒、肿瘤和自身免疫等多个重大疾病领域进行新药创制研究,发现了一批具有深入研究价值的先导化合物,8个候选新药获批进入临床研究,其中3个已完成I期进入II期临床研究,其余多个候选化合物进入全面临床前研究。围绕药物分子的优势骨架,系统开展了新的有机合成方法学研究,发展了一系列具有原始创新、高效的合成方法体系,构建了含有7000个分子的多样性“优势骨架杂环库”。 相关的药物化学和新药基础研究成果在Science、Chemical Reviews、Cell Metabolism、Nature Communications、Angewandte Chemie International Edition、Journal of Medicinal Chemistry 等国内外重要刊物上发表论文400余篇,获得国内外发明专利授权90余项,实现技术转让7项,参与15本专著章节的编写。获得“国家杰青基金”,入选中国化学会首批会士,获得第四批国家科技创新领军人才、第二十一届吴阶平-保罗·杨森医学药学奖、第十四届中国青年科技奖、第八届中国青年女科学家奖等多项荣誉,作为第一完成人获得第十六届中国药学会科学技术一等奖、2020年度上海市科技进步一等奖、2019年度上海药学科技奖一等奖等多项科技奖励,其研究团队于2018年获得了科技部创新人才推进计划重点领域创新团队称号。

    教育经历:
    1987.09-1991.07,学院,药物化学,学士
    1993.09-1996.06,学院,药物化学,硕士
    1996.09-1999.06,学院,药物化学,博士
    工作经历:
    1991.08-1993.08,山东新华制药厂四车间,助理工程师
    1999.08-2001.09,中国科学院上海药物研究所,博士后
    2001.09-2006.07,中国科学院上海药物研究所,副研究员、硕士生导师 2002.02-2002.10,美国 University of Texas Medical Branch 大学,访问科学家(Visiting Scientist)
    2005.01-2005.10,美国 University of Texas Medical Branch 大学,访问科学家(Visiting Scientist)
    2006.08-至今,中国科学院上海药物研究所化学药物研发中心,研究员
    2009.09-至今,中国科学院上海药物研究所化学药物研发中心,课题组长、博士生导师
    研究领域涉及药物化学、有机合成和计算机辅助药物设计等学科。
    1、科研成果
    (1)发展高效的合成方法学构建类药性(手性)杂环化合物库
    (2)针对重大疾病的创新药物研究
    1)抗糖尿病药物DPPIV抑制剂、SGLT2抑制剂的发现研究
    2)抗老年痴呆药物的发现研究
    3)靶向α1A-AR 的新型抗前列腺增生药物的发现研究
    4)抗HIV药物CCR5抑制剂的发现研究
    5)降脂药物PCSK9抑制剂的发现研究
    6)抗新型冠状病毒药物的发现研究
    7)抗肿瘤药物LSD1抑制剂的发现研究
    2、科研项目
    (1)2022.01-2026.12,国家自然科学基金重点项目,多维度抗冠状病毒先导化合物发现与作用机制研究,项目负责人
    (2)2020.01-2022.12,国家自然科学基金重大研究计划培育项目,降血脂活性化合物对PCSK9的表观遗传调控机制研究,项目负责人
    (3)2019.01-2020.09,中国科学院战略性先导科技专项项目,抗糖尿病新药欣格列汀的个性化研究,项目负责人
    (4)2018.01-2020.12,国家科技重大专项,靶向PCSK9的降脂候选药物DC371739的临床前研究任务,项目负责人
    (5)2017.01-2021.12,国家自然科学基金重点项目,含氮多环类药性化合物库的构建与创新药物发现及可视化研究,项目负责人
    (6)2017.01-2021.12,国家自然科学基金国际合作重点项目,金属螯合物不对称合成非天然氨基酸及其在创新药物发现与合成中的研究,项目负责人
    (7)2016.07-2019.06,上海市2016年度“科技创新行动计划”生物医药领域科技支撑项目,新型抗老年痴呆药物DC20 的临床前研究,项目负责人
    (8)2015.10-2018.12,中国科学院战略性先导科技专项项目,2型糖尿病候选药物DC291407的个性化研究,项目负责人
    (9)2013.01-2016.12,国家自然科学基金重大研究计划重点支持项目,S1P在肿瘤细胞糖脂代谢异常及非可控性炎症向肿瘤癌转化中的分子调控,项目负责人
    (10)2012.01-2015.12,国家科技重大专项,抗糖尿病类LJN系列新药候选物的临床前研究,项目负责人
    (11)2012.07-2014.06,上海市优秀学术带头人计划,手性药物优势骨架化合物库的构建与新药设计与发现研究,项目负责人
    (12)2011.01-2014.12,国家杰出青年基金,药物化学,项目负责人
    (13)2010.10-2014.09,欧盟F7框架计划SILVER项目,Small-molecule inhibitor leads versus emerging and neglected RNA viruses,中方负责人
    (14)2011.12-2013.12,科技部对欧盟合作项目, 抗肠道病毒(EV68、EV71)小分子抑制剂研究, 项目负责人
    (15)2006.11-2010.12,国家高技术研究发展计划(863)基金 JG3,DC06及DC032的研究与开发,项目负责人
    (16)2008.1-2011.12,国家自然科学基金项目,新型钾离子通道阻滞剂的发现及其亚型的选择性和功能研究,项目负责人
    1.Yaqiong Chen#, Jiang Wang#, Yibing Wang, Pengfei Wang, Zan Zhou, Rong Wu, Qian Xu, Hanyun You, Yaxin Liu, Lei Wang, Lingqin Zhou, Yuting Wu, Lihong Hu*, Hong Liu* and Yi Liu*. A Propolis-Derived Small Molecule Ameliorates Metabolic Syndrome in Obese Mice by Targeting the CREB/CRTC2 Transcriptional Complex. Nature Communications, 2022, 13, 246-265.
    2.Jiang Wang#, Jing Zhao#, Cong Yan#, Cong Xi#, Chenglin Wu, Jingxiang Zhao, Fengwei Li, Yanhua Ding, Rui Zhang, Shankang Qi, Xingjun Li, Chao Liu, Wanting Hou, Hong Chen, Yiping Wang, Dalei Wu, Kaixian Chen, Hualiang Jiang, He Huang*, and Hong Liu*. Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial. Cell Metabolism, 2022, 34, 667-680.
    3.Daqing Fang#, Xidan Wen#, Yuqi Wang, Yidan Sun, Ruibing An, Yu Zhou, Deju Ye*, Hong Liu*. Engineering of donor-acceptor-donor curcumin analogues as near-infrared fluorescent probes for in vivo imaging of amyloid-β species. Theranostics, 2022, 12, 3178-3195.
    4.Chunpu Li#, Mingbo Su#, Wei Zhu#, Weijuan Kan, Tianpeng Ge, Gaoya Xu, Shuni Wang, Li Sheng, Feng Gao, Yunfei Ye, Jiang Wang, Yubo Zhou*, Jia Li* and Hong Liu*. Structure?Activity Relationship Study of Indolin-5-yl-cyclopropanamine Derivatives as Selective Lysine Specific Demethylase 1 (LSD1) Inhibitors. Journal of Medicinal Chemistry, 2022, 65, 4335-4349.
    5.Feifei Fang, Shulei Hu, Chunpu Li, Qian Wang, Run Wang, Xu Han, Yu Zhou* and Hong Liu*. Catalytic System-Controlled Divergent Reaction Strategies for the Construction of Diversified Spiropyrazolone Skeletons from Pyrazolidinones and Diazopyrazolones. Angewandte Chemie International Edition, 2021, 60, 21327-21333.
    6.Xiaohui Wei#, Xuewu Liang#, Yazhou Li, Qi Liu, Xuyi Liu, Yu Zhou* and Hong Liu*. I2-induced cascade cyclization and dearomatization of indoles for the highly efficient synthesis of iodinated and vinylic spiroindolenines. Green Chemistry, 2021, 23, 9165-9171.
    7.Xu Han#, Ning Song#, Abdusaid Saidahmatov, Peipei Wang, Yong Wang, Xiaobei Hu, Weijuan Kan, Wei Zhu, Lixin Gao, Mingjie Zeng, Yujie Wang, Chunpu Li, Jia Li, Hong Liu*, Yubo Zhou* and Jiang Wang*. Rational Design and Development of Novel CDK9 Inhibitors for the Treatment of Acute Myeloid Leukemia. Journal of Medicinal Chemistry, 2021, 64, 14647-14663.
    8.Wenhao Dai#, Dirk Jochmans#, Hang Xie#, Hang Yang#, Jian Li, Haixia Su, Di Chang, Jiang Wang, Jingjing Peng, Lili Zhu, Yong Nian, Rolf Hilgenfeld, Hualiang Jiang, Kaixian Chen, Leike Zhang*, Yechun Xu*, Johan Neyts* and Hong Liu*. Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV?2. Journal of Medicinal Chemistry, 2022, 65, 2794-2808.
    9.Guoxue He#, Jinyu Ma#, Jianhui Zhou, Chunpu Li, Hong Liu* and Yu Zhou*. A metal-free method for the facile synthesis of indanones via the intramolecular hydroacylation of 2-vinylbenzaldehyde. Green Chemistry, 2021, 23, 1036-1040.
    10.Xiaowei Wu#, Mengdi Dai#, Rongrong Cui#, Yulan Wang, Chunpu Li, Xia Peng, Jihui Zhao, Bao Wang, Yang Dai, Dan Feng, Tianbiao Yang, Hualiang Jiang, Meiyu Geng, Jing Ai*, Mingyue Zheng*, Hong Liu*. Design, Synthesis and Biological Evaluation of Pyrazolo[3,4-d]pyridazinone Derivatives as Covalent FGFR Inhibitors. Acta Pharmaceutica Sinica B, 2021, 11, 781-794.
    11.Xuewu Liang#, Chenxia Sun#, Chunpu Li#, Haolan Yu#, Xiaohui Wei, Xuyi Liu, Wei Bao, Yuqiang Shi, Xiaochen Sun, Mirzadavlat Khamrakulov, Chenghua Yang* and Hong Liu*. Identification of Novel Fused Heteroaromatics-Based MALT1 Inhibitors by High-Throughput Screening to Treat B Cell Lymphoma. Journal of Medicinal Chemistry, 2021, 64, 9217-9237.
    12.Wenhao Dai#, Bing Zhang#, Xia-Ming Jiang#, Haixia Su#, Jian Li, Yao Zhao, Xiong Xie, Zhenming Jin, Jingjing Peng, Fengjiang Liu, Chunpu Li, You Li, Fang Bai, Haofeng Wang, Xi Cheng, Xiaobo Cen, Shulei Hu, Xiuna Yang, Jiang Wang, Xiang Liu, Gengfu Xiao, Hualiang Jiang, Zihe Rao, Lei-Ke Zhang*, Yechun Xu*, Haitao Yang*, Hong Liu*. Structure-Based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease. Science, 2020, 368, 1331-1335.
    13.Yichu Liu, Yibing Wang, Wenhao Dai, Wei Huang, Yingxia Li* and Hong Liu*. Palladium-Catalysed C(sp3)-H Glycosylation for Synthesis of C-Alkyl Glycoamino Acids. Angewandte Chemie International Edition, 2020, 59, 3491-3494.
    14.Xingjun Li#, Jiang Wang#, Xiong Xie, Wenhao Dai, Xu Han, Kaixian Chen* and Hong Liu*. Ir(III)-Catalyzed direct C-H functionalization of N-phenylacetamide with α-diazo quinones: a novel strategy for producing 2-hydroxy-2’amino-1,2’-biaryl scaffolds. Chemical Communications, 2020, 56, 3441-3444.
    15.Jingjing Peng, Chunpu Li, Mirzadavlat Khamrakulov, Jiang Wang* and Hong Liu*. Rhodium(III)-Catalyzed C?H Alkenylation: Access to Maleimide-Decorated Tryptophan and Tryptophan-Containing Peptides. Organic Letters, 2020, 22, 1535-1541.
    16.Junyou Li#, Mengqi Liu#, Yazhou Li, Dan-dan Sun, Zhihao Shu, Qian Tan, Shimeng Guo, Rongrong Xie, Lixin Gao, Hongbo Ru, Yi Zang, Hong Liu, Jia Li*, and Yu Zhou*. Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis. Journal of Medicinal Chemistry, 2020, 63, 12748-12772.
    17.Chenglin Wu#, Cong Xi#, Junhua Tong, Jing Zhao, Hualiang Jiang, Jiang Wang*, Yiping Wang* and Hong Liu*. Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives (THPBs) as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators for the treatment of hyperlipidemia. Acta Pharmaceutica Sinica B, 2019, 9, 1216-1230.
    18.Xuewu Liang, Jie Zang, Xiaoyang Li, Shuai Tang, Min Huang, Meiyu Geng, C. James Chou, Chunpu Li, Yichun Cao, Wenfang Xu, Hong Liu* and Yingjie Zhang*. Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies. Journal of Medicinal Chemistry, 2019, 62, 3898-3923.
    19.Panfeng Peng#, Huan Chen#, Ya Zhu#, Zhilong Wang#, Jian Li, Rong-Hua Luo, Jiang Wang, Liang Chen, Liu-Meng Yang, Hualiang Jiang, Xin Xie, Beili Wu*, Yong-Tang Zheng* and Hong Liu*. Structure -Based Design of 1?Heteroaryl-1,3-propanediamine Derivatives as a Novel Series of CC-Chemokine Receptor 5 Antagonists. Journal of Medicinal Chemistry, 2018, 61, 9621-9636.
    20.Feifei Fang, Chunmei Zhang, Chaofan Zhou, Yazhou Li, Yu Zhou* and Hong Liu*. Rh(III)-Catalyzed C?H Activation of Benzoylacetonitriles and Tandem Cyclization with Diazo Compounds to Substituted Benzo[de]chromenes. Organic letters, 2018, 20, 1720-1724.
    21.Xiaowei Wu, Bao Wang, Yu Zhou and Hong Liu*. Propargyl alcohols as one-carbon synthons: redox-neutral Rh (III)-catalyzed C-H bond activation for the synthesis of isoindolinones bearing a quaternary carbon. Organic Letters, 2017, 19, 1294-1297.
    22.Xiaowei Wu, Bao Wang, Shengbin Zhou, Yu Zhou*, and Hong Liu*. Ruthenium-Catalyzed Redox-Neutral [4+1] Annulation of Benzamides and Propargyl Alcohols via C-H Bond Activation. ACS catalysis, 2017, 7, 2494-2499.
    23.Wei Zhu#, Hui Chen#, Yulan Wang#, Jiang Wang, Xia Peng, Xianjie Chen, Yinglei Gao, Yulong He, Jing Ai*, Meiyu Geng, Mingyue Zheng* and Hong Liu*. Design, Synthesis, and Pharmacological Evaluation of Novel Multi-substituted Pyridin-3-amine Derivatives as Multi-Targeted Protein Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer. Journal of Medicinal Chemistry, 2017, 60, 6018-6035. 24.Yu Zhou, Jiang Wang, Zhanni Gu, Shuni Wang, Wei Zhu, Jose? Luis Acen?a*, Vadim A. Soloshonok*, Kunisuke Izawa* and Hong Liu*. Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II?III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas. Chemical Reviews, 2016, 116, 422-518.
    25.Fei Zhao#, Jing Li#, Ying Chen, Yanxin Tian, Chenglin Wu, Yanan Xie, Yu Zhou, Jiang Wang, Xin Xie* and Hong Liu*. Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective α1A-Adrenoceptor Antagonists. Journal of Medicinal Chemistry, 2016, 59, 3826-3839.
    26.Panfeng Peng, Jiang Wang, Hualiang Jiang and Hong Liu*. Rhodium(III)-Catalyzed Site-Selective C-H Alkylation and Arylation of Pyridones Using Organoboron Reagents. Organic Letters, 2016, 18, 5376-5379. 27.Diliang Guo#, Jing Li#, Henry Lin#, Yu Zhou#, Ying Chen, Fei Zhao, Haifeng Sun, Dan Zhang, Honglin Li, Brian K. Shoichet, Lei Shan, Weidong Zhang, Xin Xie*, Hualiang Jiang*, Hong Liu*. Design, Synthesis and Biological Evaluation of Novel Tetrahydroprotoberberine Derivatives (THPBs) as Selective α1A-Adrenoceptor Antagonists. Journal of Medicinal Chemistry, 2016, 59, 9489-9502.
    28.Xiaowei Wu#, Dengyou Zhang#, Shengbin Zhou, Feng Gao and Hong Liu*. Site-specific indolation of proline-based peptides via copper(II)-catalyzed oxidative coupling of tertiary amine N-oxides. Chemical Communications, 2015, 51, 12571-12573.
    29.Yong Nian, Jiang Wang, Shengbin Zhou, Shuni Wang, Hiroki Moriwaki, Aki Kawashima, Vadim A. Soloshonok* and Hong Liu*. Recyclable Ligands for the Non-Enzymatic Dynamic Kinetic Resolution of Challenging α-Amino Acids. Angewandte Chemie International Edition, 2015, 54, 12918-12922.
    30.Jiang Wang, María Sanchez-Rosello ?, Jose? Luis Acen?a, Carlos del Pozo, Alexander E. Sorochinsky, Santos Fustero*, Vadim A. Soloshonok*, Hong Liu*. Fluorine in Pharmaceutical Industry: Fluorinated Drugs Introduced to the Market in the Last Decade. Chemical Reviews, 2014, 114, 2432-2506.
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