XU Yechun

Principal Investigator
Drug Discovery and Design Center (DDDC)
 Personal Homepage

CONTACT

ycxu@simm.ac.cn

+86-21-50801267

201203

555 Zu Chong Zhi Road , Zhang Jiang Hi-Tech Park, Pudong, Shanghai

Biography

Using the methodologies of computational biology combined with the experiments, Xu Yechun has studied the interactions between small molecule and protein targets related to major diseases such as Alzheimer’s disease, the functional structures of these targets, and tried to discover the hit or lead compound targeting these proteins. So far she has 53 publications. The number of papers in which she is the first or corresponding author is 30, including one paper on Proceedings of the National Academy of Sciences of the United States of America (PNAS), two papers on Journal of the American Chemical Society, one paper on Acta Crystallographic Section D, and five papers on Journal of Medicinal Chemistry. The total number of non-self citation for all the publications is 621 and the highest one for a single paper is 126. She has applied 3 patents and one has been issued. As a principal investigator, she has undertaken projects supported by the National Natural Science Foundation of China. Her PhD dissertation was elected as the National Outstanding Doctoral Dissertations. She was awarded the CAS Novo Nordisk Great Wall Professorship and the CPA-Servier Young Investigator Awards in Medicinal Chemistry.

Research Directions
The research in our group focuses on structure and function study of the key protein associated with the pathogenesis of diseases, protein-ligand recognition and interactions, and structure-based ligand design.
Grants & Research Projects
  1. NSFC, Structure-based Drug Design, Project Leader, 2015.1-2017.12
  2. NSFC，Drug Discovery and Design to Targeting Protein-protein Interactions Involved in Alzheimer’s Disease，Project Leader，2012.1-2015.12
  3. National Science&Technology Major Project on Key New Drug Creation and Manufacturing Program，The Key Technology Development and Platform Construction for Drug Discovery Based on Structure and Function of GPCR Project team member, 2012.1-2015.12
  4. Natural Science Foundation of China (NSFC)，Mechanism Study of the Aggregation of Amyloid Beta-peptide and Drug Design Using Small Molecule as A Probe，Project Leader，2011.1-2013.12
  5. 973, Ministry of Science and Technology (MOST), China Computational Biology Investigation Based on the Structures and Interactions of Proteins，Project team member，2009.1-2013.8
  6. National Science&Technology Major Project on Key New Drug Creation and Manufacturing Program，Technology Innovation Alliance for Anti-tumor Drug Discovery，Project team member，2010.1-2012.12
  7. Science and Technology Commission of Shanghai Municipality，Shanghai Pujiang Program: Drug discovery with multiple targets of Alzheimer's disease，Project Leader，2010.7-2012.6
Achievements
  1. Molecular Dynamics Study of Traffic of Thiocholine within the Active-Site Gorge of Acetylcholinesterase
  2. Study the Flexibility of the Flap in the Active Site of BACE1 by Crystal Structures and Molecular Dynamics Simulations,and Structure-based Inhibitor Discovery
  3. Structure-based Discovery Novel and Potent Inhibitor of PDE5, and Thermodynamic and Structural Characterization of Halogen Bonding in PDE5？inhibitor Interactions
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Social Titles
 
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Awards & Honors
08/2009 CAS-Novo Nordisk Great Wall Professorship
08/2006 The National Outstanding Doctoral Dissertations
2005 SERVIER Young Investigator Awards Prize in Medicinal Chemistry
10/1999 The Third Prize of the Sixth National Session “Tiao Zhan Bei”
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Pubilcations
Full Publication List
Selected Publications

1.HX Su#, S Yao#, WF Zhao#, MJ Li#, J Liu#, WJ Shang#, H Xie, CQ Ke, HC Hu, MN Gao, KQ Yu, H Liu, JS Shen, W Tang, LK Zhang, GF Xiao, L Ni, DW Wang, JP Zuo, HL Jiang, F Bai*, Y Wu*, Y Ye*, YC Xu*. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol. Sin. 2020, 41(9):1167-1177.

2.WF Zhao#, MY Xiong#, XJ Yuan, MJ Li, HB Sun*, YC Xu*. In silico screening-based discovery of novel inhibitors of human cyclic GMP-AMP synthase: a cross-validation study of molecular docking and experimental testing. J. Chem. Inf. Model. 2020, 60(6), 3265-3276.

3.FB Huang#, HC Hu#, K Wang, CY Peng, WW Xu, Y Zhang, J Gao, YS Liu, H Zhou, RM Huang, MJ Li, JH Shen*, YC Xu*. Identification of highly selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors by a covalent-fragment-based approach. J. Med. Chem. 2020, 63(13),7052-7065.

4.WC Yin#, CY Mao#, XD Luan#, DD Shen#, QY Shen#, HX Su#, XX Wang, FL Zhou, WF Zhao, MQ Gao, SH Chang, YC Xie, GH Tian, HW Jiang, SC Tao, JS Shen, Y Jiang, HL Jiang, YC Xu*, SY Zhang*, Y Zhang*, HE Xu*. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 2020, 368, 1499–1504.

5.WH Dai#, B Zhang#, XM Jiang#, HX Su#, J Li, Y Zhao, X Xie, ZM Jin, JJ Peng, FJ Liu, CP Li, Y Li, F Bai, HF Wang, X Cheng, XB Cen, SL Hu, XN Yang, J Wang, X Liu, GF Xiao, HL Jiang, ZH Rao, LK Zhang*, YC Xu*, HT Yang*, H Liu*. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 2020, 368, 1331–1335.

6.ZM Jin#, XY Du#, YC Xu#, YQ Deng#, MQ Liu#, Y Zhao, B Zhang, XF Li, LK Zhang, C Peng, YK Duan, J Yu, L Wang, KL Yang, FJ Liu, RD Jiang, XL Yang, T You, XC Liu, XN Yang, F Bai, H Liu, X Liu, LW Guddat, WQ Xu, GF Xiao, CF Qin, ZL Shi, HL Jiang*, ZH Rao*, HT Yang*. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 2020, 582(7811), 289-293.

7.HX Su#, Y Zou#, GF Chen#, HX Dou#, H Xie, XJ Yuan, XL Zhang, NX Zhang, MJ Li, YC Xu*. Exploration of fragment binding poses leading to efficient discovery of highly potent and orally effective inhibitors of FABP4 for anti-inflammation. J. Med. Chem. 2020, 63(8), 4090-4106.

8.T Chen#, MY Xiong#, X Zong, YJ Ge, H Zhang, M Wang, GW Han, CY Yi, LM Ma, RD Ye, YC Xu*, Q Zhao,* BL Wu*. Structural basis of ligand binding modes at the human formyl peptide receptor 2. Nat. Commun. 2020, 11(1), 1208.

9.XL Zhang#, GY Dong#, H Li#, WY Chen, J Li, CL Feng, ZN Gu, FH Zhu, R Zhang, MJ Li, W Tang*, H Liu*, YC Xu*. Structure-aided identification and optimization of tetrahydro-isoquinolines as novel PDE4 inhibitors leading to discovery of an effective antipsoriasis agent. J. Med. Chem. 2019, 62(11), 5579-5593.

10.Z Wang,# XR Jiang,# XL Zhang,# GH Tian, RL Yang, JZ Wu, XL Zou, Z Liu, XJ Yang, CH Wu, J Shi, JF Li, J Suo, Y Wang, RX Zhang, ZJ Xu, XD Gong, Y He, WL Zhu, HL Jiang,* YC Xu,* JS Shen*. Pharmacokinetic-driven optimization of 4(3H)-pyrimidinones as phosphodiesterase type 5 inhibitors leading to TPN171, a clinical candidate for the treatment of pulmonary arterial hypertension. J. Med. Chem. 2019, 62(10), 4979-4990.

11.HX Su, YC Xu*. Application of ITC-based characterization of thermodynamic and kinetic association of ligands with proteins in drug design. Front. Pharmacol. 2018, 9, 1133.

12.XJ Yuan, S Raniolo, V Limongelli, YC Xu*. The molecular mechanism underlying ligand binding to the membrane-embedded site of a G-protein-coupled receptor. J. Chem. Theory Comput. 2018, 14(5), 2761-2770.

13.QF Liu#, FB Huang#, XJ Yuan#, K Wang, Y Zou, JH Shen*, YC Xu*. Structure-guided discovery of novel, potent and orally bioavailable inhibitors of lipoprotein-associated phospholipase A2. J. Med. Chem. 2017, 60 (24), 10231-10244.

14.YC Xu*, SM Cheng, JL Sussman, IS, HL Jiang. Computational studies on acetylcholinesterases. Molecules 2017, 22, 1324.

15.QF Liu#, XD Chen#, WY Chen, XJ Yuan, HX Su, JH Shen, YC Xu*. Structural and thermodynamic characterization of protein?ligand interactions formed between lipoprotein-associated phospholipase A2 and inhibitors. J. Med. Chem. 2016, 59 (10), 5115-5120.

16.WL Song, H Bajaj, C Nasrallah, HL Jiang, M Winterhalter, JP Colletier*, YC Xu*. Understanding voltage gating of providencia stuartii porins at atomic level. PLoS Comput. Biol. 2015, 11(5), e1004255.

17.J Ren#, Y He#, WY Chen, TT Chen, G Wang, Z Wang, ZJ Xu, XM Luo, WL Zhu, HL Jiang, JS Shen*, YC Xu*. Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors. J. Med. Chem. 2014, 57(8), 3588-3593.

18.N Ye#, CH Chen#, TT Chen#, ZL Song, JX He, XJ Huan, SS Song, QF Liu, Y Chen, J Ding, YC Xu,* ZH Miao,* A Zhang.* Design, synthesis and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8H)-ones bearing a functionalized longer chain appendage as novel PARP1 inhibitors. J. Med. Chem. 2013, 56(7), 2885-2903.

19.G Wang#, Z Liu#, TT Chen#, Z Wang, HY Yang, MY Zheng, J Ren, GH Tian, XJ Yang, L Li, JF Li, J Suo, RX Zhang, XR Jiang, NK Terrett, JS Shen,* YC Xu,* HL Jiang.* Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5. J. Med. Chem. 2012, 55(23), 10540-10550.

20.YX Liu#, W Zhang#, L Li#, LA Salvador, TT Chen, WY Chen, KM Felsenstein, TB Ladd, AR Price, TE Golde, JH He, YC Xu,* YX Li,* H Luesch.* Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases. J. Med. Chem. 2012, 55(23), 10749-10765.

21.YC Xu*#, MJ Li#, H Greenblatt, WY Chen, A Paz, O Dym, Y Peleg, TT Chen, X Shen, JH He, HL Jiang, IS, JL Sussman*. Flexibility of the flap in the active site of BACE1 as revealed by crystal structures and MD simulations. Acta Crystallogr. D (Biol. Crystallogr.) 2012, D68, 13-25.

22.ZJ Xu#, Z Liu#, T Chen#, TT Chen, Z Wang, GH Tian, J Shi, XL Wang, YX Lu, XH Yan, G Wang, HL Jiang, KX Chen, SD Wang,YC Xu*, JS Shen*, WL Zhu*. Utilization of halogen bond in lead optimization: a case study of rational design of potent phosphodiesterase type 5 (PDE5) inhibitors. J. Med. Chem. 2011, 54(15), 5607-5611.

23.YC Xu*, JP Colletier, M Weik, GR Qin, HL Jiang, I Silman, JL Sussman*. Long route or shortcut? a molecular dynamics study of traffic of thiocholine within the active-site gorge of acetylcholinesterase. Biophys. J. 2010, 99(12), 4003-4011.

24.YC Xu#, JP Colletier#, M Weik, HL Jiang, J Moult, I Silman, JL Sussman*. Flexibility of aromatic residues in the active-site gorge of acetylcholinesterase: X-ray vs MD. Biophys. J. 2008, 95(5), 2500-2511.

25.YC Xu#, JP Colletier#, HL Jiang, I Silman, JL Sussman, M Weik*. Induced-fit of preexisting equilibrium dynamics  Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design. Prot. Sci.2008, 17(4), 601-605.

26.YC Xu#, JH Shen#, XM Luo, WL Zhu, KX Chen, JP Ma*, HL Jiang*. Conformational transition of amyloid  -peptide. Proc. Natl. Acad. Sci. USA 2005, 102(15), 5403-5407.

27.YC Xu, FJ Barrantes, XM Luo, KX Chen, JH Shen*, HL Jiang*. Conformational dynamics of the nicotinic acetylcholine receptor channel: a 35-ns molecular dynamics simulation study. J. Am. Chem. Soc. 2005, 127(4), 1291-1299.

28.YC Xu, JH Shen*, WL Zhu*, XM Luo, KX Chen, HL Jiang*. Influence of water molecule on cation-  interaction: ab initio second order Moller-Plesset perturbation theory (MP2) calculations. J. Phys. Chem. B. 2005, 109(12), 5945-5949.

29.YC Xu, JH Shen*, XM Luo, I Silman, JL Sussman*, KX Chen, HL Jiang*. How does Huperzine A enter and leave the binding gorge of acetylcholinesterase steered molecular dynamics simulation. J. Am. Chem. Soc. 2003, 125(37), 11340-11349.

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