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专家人才

  • 姓名: 许永
  • 性别: 男
  • 职称: 研究员
  • 学历: 博士
  • 电话: 020-32093612
  • 传真: 
  • 电子邮件: xu_yong@gibh.ac.cn
  • 通讯地址 广州市开源大道190号

    简历:

  • 2011.9 – 至今    研究员,中国科学院广州生物医药与健康研究院,中科院百人计划

    2006.6 – 2011.8  博士后,结构生物学与药物发现中心,美国Van Andel研究所

    2004.8 – 2006.5  博士后,生命有机国家重点实验室,中国科学院上海有机化学研究所。

    2001.9 – 2004.7  博士, 药物发现与设计中心,中国科学院上海药物研究所。

    1998.9 – 2001.7  硕士, 辽宁师范大学化学系。

    研究领域:

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    运用计算生物学、药物化学和结构生物学等方法研究生物大分子的结构与功能以及生物大分子与小分子间的相互作用,在此基础上针对重要靶标进行药物分子设计研究。

    承担科研项目情况:

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    社会任职:

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    获奖及荣誉:

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    代表论著:

  • 在国际期刊NatureScienceNature MedicineNature Structural & Molecular BiologyCell ResearchScience SignalingJournal of Medicinal Chemistry等杂志上发表论40余篇。

    发表论文                                                                    

    1.    Wang, J.; Zou, J.X.; Xue, X.; Cai, D.; Zhang, Y.; Duan, Z.; Xiang, Q.; Yang, J.C.; Louie, M.C.; Borowsky, A.D.; Gao, A.C,; Evans, C.P.; Lam, K.S.; Xu, J.; Kung, H.J.; Evans, R.M.; Xu, Y.*; Chen, H.W.*; ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nat Med. 2016, 22: 488-496. (highlighted by Nature, Nature Review Urology)

    2.    Zheng, S.; Tang, Q.; He, J.; Du, S.; Xu, S.; Wang, C.; Xu, Y.; Lin, F.; VFFDT: A New Software for Preparing AMBER Force Field Parameters for Metal-Containing Molecular Systems. J Chem Inf Model. 2016, 56: 811-818.

    3.    Wang, Z.; Bian, H.; Bartual, S.G.; Du, W.; Luo, J.; Zhao, H.; Zhang, S.; Mo, C.; Zhou, Y.; Xu, Y.; Tu, Z.; Ren, X; Lu, X.; Brekken, R.A.; Yao, L.; Bullock, A.N.; Su, J.; Ding, K.; Structure-Based Design of Tetrahydroisoquinoline-7-Carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors. J Med Chem. 2016, May 24. [Epub ahead of print]

    4.    Song, Y.; Xue, X.; Wu, X.; Wang, R.; Xing, Y.; Yan, W.; Zhou, Y.; Qian, C-N.; Zhang, Y.; Xu, Y.*; Identification of N-phenyl-2-(N-phenylphenylsulfonamido)acetamides as new RORγ inverse agonists: Virtual screening, structure-based optimization, and biological evaluation. Eur J Med Chem, 2016, 116, 13-26.

    5.    Xue, X.; Zhang, Y.; Liu, Z.; Song, M.; Xing, Y.; Xiang, Q.; Wang, Z.; Tu, Z.; Zhou, Y.; Ding, K.; Xu, Y. Discovery of benzo[cd]indol-2(1H)-ones as potent and specific BET bromodomain inhibitors: structure-based virtual screening, optimization, and biological evaluation. J Med Chem, 2016, 59, 1565-1579.

    6.    Zhao, X.; Zhang, Z. W.; Cui, W.; Chen, S. W.; Zhou, Y.; Dong, J. H.; Jie, Y. L.; Wan, J. T.; Xu, Y.; Hu, W. H. Identification of camphor derivatives as novel M2 ion channel inhibitors of influenza A virus. Medchemcomm, 2015, 6, 727-731.

    7.    Zhang, Y.; Luo, X. Y.; Wu, D. H.; Xu, Y. ROR nuclear receptors: structures, related diseases, and drug discovery. Acta Pharmacol Sin, 2015, 36, 71-87.

    8.    Xu, S.; Mao, L.; Ding, P.; Zhuang, X.; Zhou, Y.; Yu, L.; Liu, Y.; Nie, T.; Xu, T.; Xu, Y.; Liu, J.; Smaill, J.; Ren, X.; Wu, D.; Ding, K. 1-Benzyl-4-phenyl-1H-1,2,3-triazoles improve the transcriptional functions of estrogen-related receptor gamma and promote the browning of white adipose. Bioorg Med Chem, 2015, 23, 3751-3760.

    9.    Xu, P.; Wang, J.; Xu, Y.; Chu, H.; Shen, H.; Zhang, D.; Zhao, M.; Liu, J.; Li, G. Binding modes and interaction mechanism between different base pairs and methylene blue trihydrate: a quantum mechanics study. Adv Exp Med Biol, 2015, 827, 187-203.

    10.   Xu, P.; Wang, J.; Xu, Y.; Chu, H.; Liu, J.; Zhao, M.; Zhang, D.; Mao, Y.; Li, B.; Ding, Y.; Li, G. Advancement of polarizable force field and its use for molecular modeling and design. Adv Exp Med Biol, 2015, 827, 19-32.

    11.   Wu, X.; Xu, P.; Wang, J.; Xu, Y.; Fu, T.; Zhao, M.; Zhang, D.; Liu, J.; Shen, H.; Xiu, Z.; Li, G. Theoretical studies on the folding mechanisms for different DNA G-quadruplexes. Adv Exp Med Biol, 2015, 827, 123-141.

    12.   Wu, X.; Xu, P.; Wang, J.; Xu, Y.; Fu, T.; Zhang, D.; Zhao, M.; Liu, J.; Shen, H.; Xiu, Z.; Li, G. Folding mechanisms of Trefoil Knot proteins studied by molecular dynamics simulations and Go-model. Adv Exp Med Biol, 2015, 827, 93-110.

    13.   Liu, T.; Wang, B.; Guo, J.; Zhou, Y.; Julius, M.; Njire, M.; Cao, Y.; Wu, T.; Liu, Z.; Wang, C.; Xu, Y.; Zhang, T. Role of folP1 and folP2 genes in the action of sulfamethoxazole and trimethoprim against mycobacteria. J Microbiol Biotechnol, 2015, 25, 1559-1567.

    14.   Li, Y.; Cheng, H.; Zhang, Z.; Zhuang, X.; Luo, J.; Long, H.; Zhou, Y.; Xu, Y.; Taghipouran, R.; Li, D.; Patterson, A.; Smaill, J.; Tu, Z.; Wu, D.; Ren, X.; Ding, K. N-(3-Ethynyl-2,4-difluorophenyl)sulfonamide derivatives as selective Raf inhibitors. ACS Med Chem Lett, 2015, 6, 543-547.

    15.   Zhang, Y.; Xue, X.; Jin, X.; Song, Y.; Li, J.; Luo, X.; Song, M.; Yan, W.; Song, H.; Xu, Y. Discovery of 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide derivatives as new RORgamma inhibitors using virtual screening, synthesis and biological evaluation. Eur J Med Chem, 2014, 78, 431-441.

    16.   Wang, W.; Kong, D.; Cheng, H.; Tan, L.; Zhang, Z.; Zhuang, X.; Long, H.; Zhou, Y.; Xu, Y.; Yang, X.; Ding, K. New benzimidazole-2-urea derivates as tubulin inhibitors. Bioorg Med Chem Lett, 2014, 24, 4250-4253.

    17.   Zhao, L. H.; Zhou, X. E.; Wu, Z. S.; Yi, W.; Xu, Y.; Li, S.; Xu, T. H.; Liu, Y.; Chen, R. Z.; Kovach, A.; Kang, Y.; Hou, L.; He, Y.; Xie, C.; Song, W.; Zhong, D.; Xu, Y.; Wang, Y.; Li, J.; Zhang, C.; Melcher, K.; Xu, H. E. Crystal structures of two phytohormone signal-transducing alpha/beta hydrolases: karrikin-signaling KAI2 and strigolactone-signaling DWARF14. Cell Res, 2013, 23, 436-439.

    18.   Gao, M.; Duan, L.; Luo, J.; Zhang, L.; Lu, X.; Zhang, Y.; Zhang, Z.; Tu, Z.; Xu, Y.; Ren, X.; Ding, K. Discovery and optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors. J Med Chem, 2013, 56, 3281-3295.

    19.   Cao, M.; Liu, X.; Zhang, Y.; Xue, X.; Zhou, X. E.; Melcher, K.; Gao, P.; Wang, F.; Zeng, L.; Zhao, Y.; Zhao, Y.; Deng, P.; Zhong, D.; Zhu, J. K.; Xu, H. E.; Xu, Y. An ABA-mimicking ligand that reduces water loss and promotes drought resistance in plants. Cell Res, 2013, 23, 1043-1054.

    20.   Soon, F. F.; Ng, L. M.; Zhou, X. E.; West, G. M.; Kovach, A.; Tan, M. H.; Suino-Powell, K. M.; He, Y.; Xu, Y.; Chalmers, M. J.; Brunzelle, J. S.; Zhang, H.; Yang, H.; Jiang, H.; Li, J.; Yong, E. L.; Cutler, S.; Zhu, J. K.; Griffin, P. R.; Melcher, K.; Xu, H. E. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science, 2012, 335, 85-88.

    21.   Martin, K. R.; Narang, P.; Xu, Y.; Kauffman, A. L.; Petit, J.; Xu, H. E.; Meurice, N.; MacKeigan, J. P. Identification of small molecule inhibitors of PTPsigma through an integrative virtual and biochemical approach. PLoS One, 2012, 7, e50217.

    22.   Malapaka, R. R.; Khoo, S.; Zhang, J.; Choi, J. H.; Zhou, X. E.; Xu, Y.; Gong, Y.; Li, J.; Yong, E. L.; Chalmers, M. J.; Chang, L.; Resau, J. H.; Griffin, P. R.; Chen, Y. E.; Xu, H. E. Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors. J Biol Chem, 2012, 287, 183-195.

    23.   Fu, T.; Min, H.; Xu, Y.; Chen, J.; Li, G. Molecular dynamic simulation insights into the normal state and restoration of p53 function. Int J Mol Sci, 2012, 13, 9709-9740.

    24.   Cheng, H.; Wan, J.; Lin, M. I.; Liu, Y.; Lu, X.; Liu, J.; Xu, Y.; Chen, J.; Tu, Z.; Cheng, Y. S.; Ding, K. Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein. J Med Chem, 2012, 55, 2144-2153.

    25.   Chang, S.; Zhang, L.; Xu, S.; Luo, J.; Lu, X.; Zhang, Z.; Xu, T.; Liu, Y.; Tu, Z.; Xu, Y.; Ren, X.; Geng, M.; Ding, J.; Pei, D.; Ding, K. Design, synthesis, and biological evaluation of novel conformationally constrained inhibitors targeting epidermal growth factor receptor threonine(7)(9)(0) --> methionine(7)(9)(0) mutant. J Med Chem, 2012, 55, 2711-2723.

    26.   Blind, R. D.; Pineda-Torra, I.; Xu, Y.; Xu, H. E.; Garabedian, M. J. Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy. Biochem Biophys Res Commun, 2012, 420, 839-844.

     

    2012年前论文

    27.   Zhou, X. E.; Suino-Powell, K. M.; Xu, Y.; Chan, C. W.; Tanabe, O.; Kruse, S. W.; Reynolds, R.; Engel, J. D.; Xu, H. E. The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor. J Biol Chem, 2011, 286, 2877-2885.

    28.  Xie, Q.; Wondergem, R.; Shen, Y.; Cavey, G.; Ke, J.; Thompson, R.; Bradley, R.; Daugherty-Holtrop, J.; Xu, Y.; Chen, E.; Omar, H.; Rosen, N.; Wenkert, D.; Xu, H. E.; Vande Woude, G. F. Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion. Proc Natl Acad Sci U S A, 2011, 108, 4105-4110.

    29.   Niemi, N. M.; Lanning, N. J.; Klomp, J. A.; Tait, S. W.; Xu, Y.; Dykema, K. J.; Murphy, L. O.; Gaither, L. A.; Xu, H. E.; Furge, K. A.; Green, D. R.; MacKeigan, J. P. MK-STYX, a catalytically inactive phosphatase regulating mitochondrially dependent apoptosis. Mol Cell Biol, 2011, 31, 1357-1368.

    30.   Miao, J.; Choi, S. E.; Seok, S. M.; Yang, L.; Zuercher, W. J.; Xu, Y.; Willson, T. M.; Xu, H. E.; Kemper, J. K. Ligand-dependent regulation of the activity of the orphan nuclear receptor, small heterodimer partner (SHP), in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes. Mol Endocrinol, 2011, 25, 1159-1169.

    31.   Martin, K. R.; Xu, Y.; Looyenga, B. D.; Davis, R. J.; Wu, C. L.; Tremblay, M. L.; Xu, H. E.; MacKeigan, J. P. Identification of PTPsigma as an autophagic phosphatase. J Cell Sci, 2011, 124, 812-819.

    32.   He, Y.; Xu, Y.; Zhang, C.; Gao, X.; Dykema, K. J.; Martin, K. R.; Ke, J.; Hudson, E. A.; Khoo, S. K.; Resau, J. H.; Alberts, A. S.; MacKeigan, J. P.; Furge, K. A.; Xu, H. E. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci Signal, 2011, 4, ra44.

    33.   Powell, E.; Huang, S. X.; Xu, Y.; Rajski, S. R.; Wang, Y.; Peters, N.; Guo, S.; Xu, H. E.; Hoffmann, F. M.; Shen, B.; Xu, W. Identification and characterization of a novel estrogenic ligand actinopolymorphol A. Biochem Pharmacol, 2010, 80, 1221-1229.

    34.   Melcher, K.; Xu, Y.; Ng, L. M.; Zhou, X. E.; Soon, F. F.; Chinnusamy, V.; Suino-Powell, K. M.; Kovach, A.; Tham, F. S.; Cutler, S. R.; Li, J.; Yong, E. L.; Zhu, J. K.; Xu, H. E. Identification and mechanism of ABA receptor antagonism. Nat Struct Mol Biol, 2010, 17, 1102-1108.

    35.   Xu, Y.; Zhang, T.; Chen, M. Combining 3D-QSAR, docking, molecular dynamics and MM/PBSA methods to predict binding modes for nonsteroidal selective modulator to glucocorticoid receptor. Bioorg Med Chem Lett, 2009, 19, 393-396.

    36.   Melcher, K.; Ng, L. M.; Zhou, X. E.; Soon, F. F.; Xu, Y.; Suino-Powell, K. M.; Park, S. Y.; Weiner, J. J.; Fujii, H.; Chinnusamy, V.; Kovach, A.; Li, J.; Wang, Y.; Li, J.; Peterson, F. C.; Jensen, D. R.; Yong, E. L.; Volkman, B. F.; Cutler, S. R.; Zhu, J. K.; Xu, H. E. A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors. Nature, 2009, 462, 602-608.

    37.   Tao, Y. G.; Xu, Y.; Xu, H. E.; Simons, S. S., Jr. Mutations of glucocorticoid receptor differentially affect AF2 domain activity in a steroid-selective manner to alter the potency and efficacy of gene induction and repression. Biochemistry, 2008, 47, 7648-7662.

    38.   Suino-Powell, K.; Xu, Y.; Zhang, C.; Tao, Y. G.; Tolbert, W. D.; Simons, S. S., Jr.; Xu, H. E. Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol. Mol Cell Biol, 2008, 28, 1915-1923.

    39.   Kruse, S. W.; Suino-Powell, K.; Zhou, X. E.; Kretschman, J. E.; Reynolds, R.; Vonrhein, C.; Xu, Y.; Wang, L.; Tsai, S. Y.; Tsai, M. J.; Xu, H. E. Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor. PLoS Biol, 2008, 6, e227.

    40.   Wang, R.; Lin, F.; Xu, Y.; Cheng, T. I-SOLV: a new surface-based empirical model for computing solvation free energies. J Mol Graph Model, 2007, 26, 368-377.

    41.   Guo, D.; Sarkar, J.; Suino-Powell, K.; Xu, Y.; Matsumoto, K.; Jia, Y.; Yu, S.; Khare, S.; Haldar, K.; Rao, M. S.; Foreman, J. E.; Monga, S. P.; Peters, J. M.; Xu, H. E.; Reddy, J. K. Induction of nuclear translocation of constitutive androstane receptor by peroxisome proliferator-activated receptor alpha synthetic ligands in mouse liver. J Biol Chem, 2007, 282, 36766-36776.

    42.   Cheng, T.; Zhao, Y.; Li, X.; Lin, F.; Xu, Y.; Zhang, X.; Li, Y.; Wang, R.; Lai, L. Computation of octanol-water partition coefficients by guiding an additive model with knowledge. J Chem Inf Model, 2007, 47, 2140-2148.

    43.   Xu, Y.; Wang, R. A computational analysis of the binding affinities of FKBP12 inhibitors using the MM-PB/SA method. Proteins, 2006, 64, 1058-1068.

    44.   Ma, D.; Jiang, Y.; Chen, F.; Gong, L. K.; Ding, K.; Xu, Y.; Wang, R.; Ge, A.; Ren, J.; Li, J.; Li, J.; Ye, Q. Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. J Med Chem, 2006, 49, 456-458.

    45.   Niu, C.; Xu, Y.; Xu, Y.; Luo, X.; Duan, W.; Silman, I.; Sussman, J. L.; Zhu, W.; Chen, K.; Shen, J.; Jiang, H. Dynamic mechanism of E2020 binding to acetylcholinesterase: a steered molecular dynamics simulation. J Phys Chem B, 2005, 109, 23730-23738.

     

    46.   Xu, Y.; Liu, H.; Niu, C.; Luo, C.; Luo, X.; Shen, J.; Chen, K.; Jiang, H. Molecular docking and 3D QSAR studies on 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes based on the structural modeling of human CCR5 receptor. Bioorg Med Chem, 2004, 12, 6193-6208.