师资队伍

王任小(主任,校内双聘)药物化学, 研究员, 博士生导师

特聘研究员,药学院;药物化学

教育经历

1989.09 – 1994.07 北京大学化学与分子工程学院, 物理化学专业,理学学士1994.09 – 1999.07 北京大学化学与分子工程学院, 物理化学专业,理学博士

1999.09 – 2000.08 美国加州大学洛杉矶分校化学系, 博士后

2000.09 – 2001.08 美国乔治敦大学医学院,博士后


工作经历

2001.09 –2005.07美国密西根大学医学院,Research Investigator2005.08 –2019.12中国科学院上海有机化学研究所,生命有机化学国家重点实验室,研究员

2020.01 –至今 复旦大学药学院,特聘研究员


获奖及荣誉

先后获得药明康德“生命化学研究奖”、中国化学会“青年计算化学家奖”、中国药学会“施维雅青年药物化学家”等多项国内知名奖项,并于2012年获得国际化学信息学会“Corwin Hansch Award”,系中国科学家首次获得这一国际奖项。目前担任中国化学会计算机化学专业委员会副主任委员、生物物理化学专业委员会副主任委员、化学生物学专业委员会委员以及上海市药学会药物化学专业委员会委员。受邀担任J. Chem. Inf. Model.、ChemMedChem、Molecular Informatics等国内外多家刊物编委。2017年获得国家自然科学基金委医学部“国家杰出青年”科学基金项目资助。


研究方向

1.研究和发展分子靶向药物设计的新理论、新方法。2.运用分子模拟技术研究重要生物大分子体系或活性小分子化合物的作用机制。

3.运用分子设计技术,针对新靶标发现和优化先导化合物,发展创新药物。


科研成果

擅长发展分子靶向药物设计的新理论和新方法,代表性成果有对蛋白-配体相互作用打分函数的研究、蛋白-配体复合物数据库、配体分子的自动设计方法等。所发展的药物设计软件在70多个国家拥有12000余名注册用户,其中许多来自国际著名的大学、研究所以及大型医药公司,形成了广泛的国际影响,累计被他人成功应用1400余次。同时在实践中应用药物设计技术,选择Bcl-2家族等蛋白-蛋白作用体系作为靶标,成功获得了若干类抗肿瘤活性先导化合物。学术生涯已发表SCI索引论文140余篇,Google引用超过13400次(H指数为46),并获得国家发明专利授权和软件著作权40余项。


近10年来代表性论文

(1) Feng, G. Q.; Zhang, X. Y.; Li, Y.;Wang, R. X.*“Analysis of the Binding Sites on BAX and the Mechanism of BAX Activators Through Extensive Molecular Dynamics Simulations”,J. Chem. Inf. Model.(ASAP) DOI: 10.1021/acs.jcim.0c01420

(2) Yang, Q. F.; Qiu, X. X.; Zhang, X. Z.; Yu, Y. T.; Li, N.; Wei, X.; Feng, G. Q.; Li, Y.; Zhao, Y. X.*;Wang, R. X.*“Optimization of Beclin 1-Targeting Stapled Peptides by Staple Scanning Leads to Enhanced Antiproliferative Potency in Cancer Cells”,J. Med. Chem.2021, 64(18), 13475–13486.

(3) Li, Y.; Fan, W. J.; Gong, Q. N.; Tian, J.; Zhou, M.; Li, Q.; Uwituze, L. B.; Zhang, Z. C.*; Hong, R.*;Wang, R. X.*“Structure-Based Optimization of 3-phenyl-N-(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors”,J. Med. Chem.2021, 64(14),10260-10285.

(4)Wang, R. X.;*Zhou, M; Ma, HL; Qiao, YB; Li, QS.* “The Role of Chronic Inflammation in Various Diseases and Anti-inflammatory Therapies Containing Natural Products”.ChemMedChem,2021, 16(10), 1576-1592.

(5) Du, Y.;Wang, R. X.*“Revealing the Unbinding Kinetics and Mechanism of Type I and Type II Protein Kinase Inhibitors by Local-Scaled Molecular Dynamic Simulations”,J. Chem. Theory Comput.2020, 16(10), 6620−6632.

(6) Li, Y.; * Gao, Y. D.; Holloway, M. K,;Wang, R. X.*“Prediction of the Favorable Hydration Sites in a Protein Binding Pocket and Its Application to Scoring Function Formulation”,J. Chem. Inf. Model.,2020, 60(9), 4359−4375.

(7) Li, Y.;* Sun, Y. P.; Song, Y. P.; Dai, D. C.; Zhao, Z. X.; Zhang, Q.; Zhong, W. G.; Hu, L. Y.; Ma, Y. L.; Li, X.;*Wang, R. X.*“Fragment-Based Computational Method for Designing GPCR Ligands”,J. Chem. Inf. Model.2020, 60(9), 4339−4349.

(8) Su, M. Y.; Feng, G. Q.; Liu, Z. H.; Li, Y.;Wang, R. X.*“Tapping on the Black Box: How is the Scoring Power of a Machine-Learning Scoring Function Depended on the Training Set?”,J. Chem. Inf. Model.2020, 60(3), 1122-1136.

(9) Li, Q.;# An, R.;#, Xu, Y. C.; Zhou, M.; Li, Y.;* Guo, C.*;Wang, R. X.*, “Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells”,Bioorg. Med. Chem. Lett.2020, 30(10), 127114.

(10) Walters, W. P.*;Wang, R. X.*“New Trends in Virtual Screening” (Editorial),J. Chem. Inf. Model.2020, 60(9), 4109−4111.

(11) Yang, Q. F.; Su, M. Y.; Li, Y.;Wang, R. X.*“Revisiting the Relationship Between Correlation Coefficient, Confidence Level, and Sample Size”,J. Chem. Inf. Model.2019, 59(11), 4602-4612.

(12) Su, M. Y.; Yang, Q. F.; Du, Y.; Feng, G. Q.; Liu, Z. H.; Li, Y.;*Wang, R. X.*“Comparative Assessment of Scoring Functions: The CASF-2016 Update”,J. Chem. Inf. Model.2019, 59, 895−913.

(13) Li, Y.; Su, M. Y.; Liu, Z. H.; Li, J.; Liu, J.; Han, Li.;Wang, R. X.*'Assessing Protein-Ligand Interaction Scoring Functions with the CASF-2013 Benchmark',Nat. Protocol,2018, 13, 666-680.

(14) Wong, K. W.; Qu, Y.-Q.; Gordillo-Martinez, F.; Law, Y. K.; Han, Y.; Wu, A.-G.; Zeng, W.; Lam, W. K.; Ho, C.; Mok, S. W.; He, H.-Q.;Wang, R. X.*, '2-aminoethoxy diphenylborane (2-APB) sensitizes anti-tumor effect of bortezomib (BZM) via suppression of calcium-mediated autophagy',Cell Death & Disease,2018, 9, 361.

(15) Liu, Z. H.; Su, M. Y.; Han, Li.; Liu, J.; Yang, Q. F.; Li, Y.;*Wang, R. X.*' Forging the Basis for Developing Protein?Ligand Interaction Scoring Functions',Acc. Chem. Res.2017, 50(2), 302–309.

(16) Zheng, S. Q.; Xu, S. F.; Wang, G. T.; Tang, Q.; Jiang, X. N.; Li, Z. T.; Xu, Y.;Wang, R. X.*, Lin, F.* 'Proposed Hydrogen-Bonding Index of Donor or Acceptor Reflecting Its Intrinsic Contribution to Hydrogen-Bonding Strength',J. Chem. Inf. Model.2017, 57(7), 1535–1547.

(17) Liu, J.; Liu, Z. H.; Li, J.; Li, Y.;Wang, R. X.*'Enhance the performance of current scoring functions with the aid of 3D protein-ligand interaction fingerprints',BMC Bioinformatics,2017, 18, 343-364.

(18) Li, Y.; Zhao, Z. X.; Liu, Z. H.;Wang, R. X.*'AutoT&T v.2: An Efficient and Versatile Tool for Lead Struc-ture Generation and Optimization',J. Chem. Inf. Model.,2016, 56(2), 435–453.

(19) Zhou, M.; Li, Q.;Wang, R.-X.*'Current Experimental Methods for Characterizing Protein-Protein Interactions',ChemMedChem,2016, 11(8), 738-756.

(20) Li, Y.-F.; Yu, B.;Wang, R.-X.*, 'Efficient synthesis of rottlerin and its two subunits',Tetrahedron Lett.2016, 57, 1856–1859.

(21) Xu, M.; Liu, C.; Zhou, M.; Li, Q.;Wang, R. X.*; Kang, J. W.*, “Screening of Small-Molecule Inhibitors of Protein–Protein Interaction with Capillary Electrophoresis Frontal Analysis”,Anal. Chem.,2016, 88(16), 8050-8057.

(22) Liu; Z.-H.; Li, Y.; Han, L.; Li, J.; Liu, J.; Zhao, Z.-X.; Nie, W.; Liu, Y.-C.;Wang, R.-X.*'PDB-wide Collection of Binding Data: Current Status of the PDBbind Database',Bioinformatics,2015, 31(3), 405-412.

(23) Liu, J.;Wang, R.-X.*'Classification of Current Scoring Functions',J. Chem. Inf. Model.2015, 55(3),475–482.

(24) Liu, Z. H.; Li, J.; Liu, J.; Liu, Y. C.; Nie, W.; Han, L.; Li, Y.;Wang, R.-X.*' Cross-Mapping of Protein-Ligand Binding Data between ChEMBL and PDBbind',Mol. Info.2015, 34(8), 568–576.

(25) Li, Y.-L.; Qi, X.-Y.; Jiang, H.; Deng, X.-D.; Dong, Y.-P.; Ding, T. B.; Zhou, L.; Men, P.; Chu, Y.;Wang, R.-X.;*Jiang, X.-C.;* Ye, D.-Y.* 'Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors',Bioorg. Med. Chem.2015, 23, 6173–6184.

(26) Li, Y.-F.; Yu, B.; Sun, J.-S.;Wang, R.-X.*'Efficient synthesis of baicalin and its analogs',Tetrahedron Lett.,2015, 56(24), 3816–3819.

(27) Li, Y.; Liu, Z. H.; Han, L.; Li, J.; Liu, J.; Zhao, Z. X.; Li, C. K.;Wang, R. X.*'Comparative Assessment of Scoring Functions on an Updated Benchmark: I. Compilation of the Test Set',J. Chem. Inf. Model.2014, 54 (6), 1700–1716.

(28) Li, Y.; Han, L.; Liu, Z. H.;Wang, R. X.*, 'Comparative Assessment of Scoring Functions on an Updated Benchmark: II. Evaluation Methods and General Results',J. Chem. Inf. Model.2014, 54 (6), 1717–1736.

(29) Yang, C. W.; Chen, S.; Zhou, M.; Li, Y.; Li, Y. F.; Zhang, Z. X.; Liu, Z.; Ba, Q.; Li, J. Q.; Wang, H.; Yang, X. M.*, Ma, D. W.*,Wang, R. X.*, 'Development of 3-Phenyl-N- (2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide Compounds as Inhibitors of Anti-apoptotic Bcl-2 Family Proteins',ChemMedChem,2014, 9(7), 1436–1452.

(30) Deng, X.; Lin, F.; Zhang, Y.; Li, Y.; Zhou, L.; Lou, B.; Li, Y.; Dong, J.; Ding, T. B.; Jiang, X. C.;Wang, R. X.*; Ye, D. Y.* 'Identification of Small Molecule Sphingomyelin synthase inhibitors',Eur. J. Med. Chem.2014, 73, 1-7.

(31) Li, Y.; Liu, Z.; Han, L.; Li, C.;Wang, R.*Mining the Characteristic Interaction Patterns on Protein-Protein Binding Interfaces,J. Chem. Inf. Model.,2013, 53(9), 2437-2447.

(32) Ding, X.; Li, Y.; Lv, L.; Zhou, M.; Han, L.; Zhang, Z.; Ba, Q.; Li, J.; Wang, H.; Liu, H.;*,Wang, R.*, 'De novo Design, Synthesis and Evaluation of Benzylpiperazine Derivatives as Highly Selective Binders of Mcl-1',ChemMedChem,2013, 8(12), 1986-2014.

(33) Han, L.;Wang, R.*, 'Rise of the Selective Inhibitors of Anti-Apoptotic Bcl-2 Family Proteins',ChemMedChem,2013, 8(9), 1437-1440.

(34) Zhao, Z.; Zhang, Z.; Li, Y.; Zhou, M.; Li, X.; Yu, B.;Wang, R*, 'Probing the Key Interactions Between Human Atg5 and Atg16 Proteins: A Prospective Application of Molecular Modelling',ChemMedChem,2013, 8, 1270 – 1275. (back cover)

(35) Xu, Y.; Zhou, M.; Li, Y.; Li, C.; Zhang, Z.; Yu, B*;Wang, R*, 'Characterization of the Stereochemical Structures of 2H-thiazolo[3,2-a]-Pyrimidine Compounds and Their Binding Affinities to Anti-Apoptotic Bcl-2 Family Proteins',ChemMedChem,2013, 8, 1345 – 1352.

(36) Zhou, M.;Wang, R. X.*'Small-Molecule Regulators of Autophagy and Their Potential Therapeutic Applications',ChemMedChem,2013, 8, 694-707.

(37) Shi, S.; Han, L.; Zhou, M.; Li, Y.; Liu, Z.; Yu, B.;Wang, R. X.*, 'Synthesis of 4-(2-Phenylhydrazono)-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5(4H)-one Compounds and Characterization of Their Affinities to Anti-apoptotic Bcl-2 Family Proteins',Chin. J. Chem.2013, 31, 1133-1138

(38) Shi, Z. M.; Li, Y.; Liu, Z. H.; Mi, J.;Wang, R. X.*'Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model',Molecular Informatics,2012, 13(11-12), 793-807.

(39) Li, Y.; Zhao, Y.;Wang, R.*'Automatic Tailoring and Transplanting: A Practical Method that Makes Virtual Screening More Useful',J. Chem. Inf. Model.,2011, 51, 1474–1491.

(40) Zhou, B.; Li, X.; Li, Y.; Xu, Y.; Zhang, Z.; Zhou, M; Zhang, X.; Liu, Z.; Zhou, J.; Cao, C.; Yu, B.;*Wang, R.,* 'Discovery and Development of 2H-thiazolo[3,2-a]pyrimidine Derivatives as General Inhibitors of Bcl-2 Family Proteins',ChemMedChem,2011, 6, 904–921.

(41) Lou, J.-P.; Liu, Z.; Li, Y.; Zhou, M.; Zhang, Z.-X., Zheng, S.;Wang, R.-X.*; Li, J*. 'Synthesis and anti-tumor activities of N'-benzylidene-2-(4-oxothieno[2,3-d] pyrimidin-3(4H)-yl) acetohydrazone derivatives', Bioorgan.Med. Chem. Lett.2011, 21, 6662–6666.

(42) Zhang, Y.; Lin, F.; Deng, X.-D.,Wang, R.-X.*, Ye, D.-Y.*, 'Molecular Modeling of the Three-Dimensional Structure of Human Sphingomyelin Synthase',Chinese J. Chem.2011, 29, 1567-1575.