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Resume/summaryŁ

Senior Research Scientist
Gilead

Education
1984:
B.S., Physical Chemistry, Department of Chemistry, Xiamen University, Xiamen, Fujian, P.R. China. Ph.D. in Biophysics/Physical Chemistry with Prof. Robert C. Matthews, Department of Chemistry, the Pennsylvania State University, USA Postdoctoral Fellow with Prof. Fred Cohen, Department of Pharmaceutical Chemistry, University of California, San Francisco, USA

Professional Experience
1993-1997: Postdoctoral researcher, molecular modeling and structure-based drug discovery,
University of California, San Francisco with Prof. Fred Cohen Scientist and Sr. Scientist, molecular modeling and structure-based drug discovery, Gilead Sciences, Foster City, California Membership: American Chemical Society

Patents:
co-inventor of following issued patents
US 5,739,170: Inhibitors of metazoan parasite proteases
US 6,194,421: Inhibitors of metazoan parasite proteases.
US 7,253,180: Pre-organized tricyclic integrase inhibitor compounds.
US 7,407,965: Phosphonate analogs for treating metabolic diseases
US 7,417,055: Kinase inhibitory phosphonate analogs
US 7,427,624: Purine nucleoside phosphorylase inhibitory phosphonate compounds
US 7,427,636: Inosine monophosphate dehydrogenase inhibitory phosphonate compounds
US 7,429,565: Antiviral phosphonate analogs
US 7,432,261: Anti-inflammatory phosphonate compounds
US 7,452,901: Anti-cancer phosphonate analogs
US 7,462,608: Non nucleoside reverse transcriptase inhibitors
US 7,470,724: Phosphonate compounds having immuno-modulatory activity

Oral Presentations
Characterizing Urea-induced Folding Mechanism of the α Subunit of Tryptophan Synthase by
Site-directed Mutagenesis and Kinetics
X. Chen and C.R. Matthews
American Biophysical Society Annual Meeting (1992) San Francisco, USA
Structure-Based Anti-Parasitic Drug Development X. Chen, R. Li, Z. Li, C. Ring, B. Gong, J. Dominquez, E. Davidson, W. Roush, P. Rosenthal, G. Kenyon, J. McKerrow, I. Kuntz, F. Cohen American Crystallography Union Annual Meeting (1996) Montreal, Canada Discovery of Novel Hydrophobic Interaction Between Influenza Neuraminidase and Oseltamivir and Its implication on Virtual Screening X. Chen, J.M. Chen, S. Swaminathan SBS 11th Annual Conference & Exhibition: Drug Discovery: From Targets to Candidates (2005) Geneva, Switzerland Structural Basis for Tamiflu’s Role in Influenza Treatment and Prevention X. Chen CABS (Chinese-American BioPharmaceutial Society) seminar on Avian Flu Research (2006) Mountain View, CA, USA and CBA (Chinese Bioscience Association) seminar on Avian Flu (2006) Mountain View, CA, USA Tamiflu: Unusual Hydrophobic Interaction and Its Implication on Drug Discovery X. Chen Theory and Applications of Computational Chemistry 2008 Shanghai, China Chair, session of Cheminformatics and Drug Design Modeling Binding Modes of HIV Integrase Inhibitors X. Chen, S. Swaminathan, J. Chen The 23rd Annual Meeting of the Groups Studying the Structures of AIDS-Related Systems and Their Application to Targeted Drug Design by NIH (2009) Bethsda, Maryland, USA Modeling Binding Modes of HIV Integrase Inhibitors X. Chen, S. Swaminathan, J. Chen ACS Fall 2009 National Meeting (2009) Washington, DC, USA Modeling HIV Integrase Inhibition: A Tale of Two Binding Modes X. Chen, S. Swaminathan, J. Chen NIDDK seminar (2009, hosted by Dr. W. Yang), NIH, Bethesda, Maryland, USA A Tale of Two Drugs: Structure-based Discovery of Neuraminidase Inhibitors Tamiflu (达菲) and Relenza as Anti-Influenza Agents Xiaowu Chen Seminar (2009, hosted by Prof. Michael Yang), Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, China Modeling Hypothesis and Validation of Scaffold-Dependent SAR of HCV NS3 Protease Inhibition Xiaowu Chen, Chris Sheng, Choung Kim, Huiling Yang, William Delaney, Todd Appleby, S. Swaminathan ACS Spring National Meeting (2010), San Francisco, USA Discovery of A Novel Hydrophobe-Polar π Interaction in Influenza Neuraminidase Inhibition by Tamiflu (达菲) and Implication on Structure-based Drug Development Xiaowu Chen Seminar (2010, hosted by Prof. Luhua Lai), Department of Chemistry, Peking University, Beijing, China Publications
1. Mutational analysis of Protein Folding Mechanisms
P. A. Jennings, S. M. Saalau-Bethell, B. E. Finn, X. Chen, and C.R. Matthews Methods in Enzymology (1991) 202, 113. 2. Analysis of "Toward A Simplification of the Protein Folding Problem: A Stabilizing Polyalanine α-Helix Engineered in T4 Lysozyme" by Zhang et al. X. Chen and C. R. Matthews Chemtracts (1991) 2, 260. 3. Principles of Protein Stability I: reversible unfolding of proteins - kinetic and thermodynamic analysis B. E. Finn, X. Chen, P. A. Jennings, S. M. Saalau-Bethell, and C. R. Matthews Protein Engineering: A Practical Approach (1992, Rees, A.R., Wetzel, R., & Sternberg, J.E., eds.) IRL Press, Oxford, UK 4. Amino Acid Replacements Can Selectively Affect the Interaction Energy of Autonomous Folding Units in the α Subunit of Tryptophan Synthase X. Chen, R. Rambo, and C. R. Matthews Biochemistry (1992, accelerated publication) 31, 2219. 5. Mutagenic Analysis of the Interior Packing of an α/β Barrel Protein. Effects on the Stabilities and Rates of Interconversion of the Native and Partially Folded Forms of the α Subunit of Tryptophan Synthase T. Tsuji, B. A. Chrunyk, X. Chen, and C. R. Matthews Biochemistry (1993) 32, 5566. 6. Thermodynamic Properties of the Transition State for the Rate-Limiting Step in the Folding of the α Subunit of Tryptophan Synthase. X. Chen and C. R. Matthews Biochemistry (1994) 33, 6356 7. Characterization of a Plasmodium vivax Cysteine Proteinase Gene Identifies Uniquely Conserved Amino Acids that May Mediate the Substrate Specificity of Malarial Hemoglobinases P. Rosenthal, C. Ring, X. Chen, and F. Cohen Journal of Molecular Biology (1994) 241, 312 8. Anti-malarial Drug Development Using Models of Enzyme Structure Z. Li, X. Chen, E. Davidson, O. Zwang, C. Mendis, C. Ring, W. Roush, G. Fegley, R. Li, P. Rosenthal, G. Lee, G. Kenyon, I. Kuntz, and F. Cohen Chemistry & Biology (1994) 1, 31 9. In Vitro Anti-malarial Activity of Chalcones and Their Derivatives R. Li, X. Chen, B. Gong, J. Dominguez, E. Davidson, R. Miller, E. Nuzum, J. McKerrow, I. Kuntz, G. Kenyon, and F. Cohen Journal of Medicinal Chemistry (1995) 38, 5031 10. Structure-based Design of Parasitic Protease Inhibitors R. Li, X. Chen, B. Gong, Z. Li, E. Davidson, G. Kurzban, R. Miller, E. Nuzum, J.
McKerrow, R. Fletterick, S. Gillmor, C. Craik, I. Kuntz, F. Cohen, and G. Kenyon
Journal of Bioorganic and Medicinal Chemistry (1996) 4, 1421
11. Meeting review: the Second meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP2), Asilomar, California, December 13-16, 1996. R.L. Dunbrack Jr, D.L. Gerloff, M. Bower, X. Chen, O. Lichtarge, F.E. Cohen Folding and Design (1997) 2:R27 12. Molecular Modeling of Cysteine Proteases from Leishmania major and Development of Novel, Nonpeptidic Inhibitors P. Selzer, X. Chen, V. Chan, M. Cheng, G. Kenyon, I. Kuntz, J Sakanari, F. Cohen, and J. McKerrow Experimental Parasitology (1997) 87,212 13. Structure-Activity Relationship Studies of Novel Carbocyclic Influenza Neuraminidase Inhibitors C. U. Kim, W. Lew, M. A. Williams, H. Wu, L. Zhang, X. Chen, P. A, Escarpe, D. B. Mendel, W. G. Laver, and R. C. Stevens Journal of Medicinal Chemistry (1998) 41, 2451 14. A new series of C3-aza carbocyclic influenza neuraminidase inhibitors: synthesis and inhibitory activity. W. Lew, H. Wu, D. B. Mendel, P. A. Escarpe, X. Chen, W. G. Laver, B. J. Graves, and C. U. Kim Bioorg Med Chem Lett (1998) 8, 3321 15. Synthesis and evaluation of 1,4,5,6-tetrahydropyridazine derivatives as influenza neuraminidase inhibitors
L. Zhang, M. A. Williams, D. B. Mendel, P. A. Escarpe, X. Chen, K. Y. Wang, B. J.
Graves, G. Lawton, and C. U. Kim
Bioorg Med Chem Lett. (1999) 9,1751
16. Neuraminidase Inhibitors as Anti-Influenza Agents C. U. Kim, X. Chen, and D. B. Mendel
Antiviral Chemistry & Chemotherapy (1999) 10, 141
17. Chalcone, acyl hydrazide, and related amides kill cultured Trypanosoma brucei brucei Troeberg, L., X. Chen, T. M. Flaherty, R. E. Morty, M. Cheng, H. Hua, C. Springer, J. H. McKerrow, G. L. Kenyon, J. D. Lonsdale-Eccles, T. H. Coetzer and F. E. Cohen Mol Med (2000) 6, 660-9. 18. Carbocyclic influenza neuraminidase inhibitors possessing a C3-cyclic amine side chain: synthesis and inhibitory activity Lew, W., H. Wu, X. Chen, B. J. Graves, P. A. Escarpe, H. L. MacArthur, D. B. Mendel and C. U. Kim Bioorg Med Chem Lett (2000) 10, 1257-60. 19. Discovery and Development of GS 4104 (oseltamivir): An Orally Active Influenza Neuraminidase Inhibitor. W. Lew, X. Chen, C. U. Kim Current Medicinal Chemistry (2000) 7, 663 20. Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms
Douglas, J. L., M. L. Panis, E. Ho, K. Y. Lin, S. H. Krawczyk, D. M. Grant, R. Cai, S.
Swaminathan, X. Chen and T. Cihlar
Antimicrob Agents Chemother (2005) 49, 2460-6.
21. Structural Basis of Neuraminidase Inhibitors with Broad Spectrum Activity against Influenza X. Chen Trends in Bio/Pharmaceutical Industry (2006) 27-31. 22. Suppression of HIV-1 protease inhibitor resistance by phosphonate-mediated solvent anchoring
Cihlar, T., G.X. He, X. Liu, J.M. Chen, M. Hatada, S. Swaminathan, M.J. McDermott, Z.Y.
Yang, A. S. Mulato, X. Chen, S.A. Leavitt, K.M. Stray and W. A. Lee
J Mol Biol (2006) 363, 635-47.
23. Design, synthesis, and SAR studies of novel and highly active tri-cyclic HIV integrase inhibitors Jin, H., R. Z. Cai, L. Schacherer, S. Jabri, M. Tsiang, M. Fardis, X. Chen, J. M. Chen and C. U. Kim Bioorg Med Chem Lett (2006) 16, 3989-92. 24. Tricyclic HIV integrase inhibitors: potent and orally bioavailable C5-aza analogs. Jin, H., M. Wright, R. Pastor, M. Mish, S. Metobo, S. Jabri, R. Lansdown, R. Cai, P. Pyun, M. Tsiang, X. Chen and C. U. Kim Bioorg Med Chem Lett (2008) 18, 1388-91. 25. Modeling, Analysis and Validation of a Novel HIV Integrase Structure Provides Insights into the Binding Modes of Potent Integrase Inhibitors
X. Chen, M. Tsiang, F. Yu, M. Hung, G.S. Jones, A. Zeynalzadegan, X. Qi, H. Jin, C.U.
Kim, S. Swaminathan and J.M. Chen
Journal of Molecular Biology (2008) 380, 504-19
JMB Top Cited Article 2008-2010
26. Tricyclic HIV integrase inhibitors: VI. SAR studies of 'benzyl flipped' C3-substituted pyrroloquinolines S. Metobo S, M. Mish, H. Jin, S. Jabri, R. Lansdown, X. Chen, M. Tsiang, M. Wright, C. Kim Bioorg Med Chem Lett. (2009) 19, 1187-90 27. Tricyclic HIV integrase inhibitors V. SAR studies on the benzyl moiety. H. Jin, S. Metobo, S. Jabri, M. Mish, R. Lansdown, X. Chen, M. Tsiang, M. Wright, C. Kim Bioorg Med Chem Lett. (2009) 19, 2263-5 28. Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase GS. Jones, F. Yu, A. Zeynalzadegan, J. Hesselgesser, X. Chen, J. Chen, H. Jin, C. Kim, M. Wright, R. Geleziunas R, M. Tsiang Antimicrob Agents Chemother. (2009) 53, 1194-203 29. Discovery of novel phosphonate derivatives as hepatitis C virus NS3 protease inhibitors X. Sheng, H. Pyun, K. Chaudhary, J. Wang, E. Doerffler, M. Fleury, D. McMurtrie, X. Chen, W. Delaney, C. Kim Bioorg Med Chem Lett. (2009) 19, 3453-7 30. Affinities between the binding partners of the HIV-1 integrase dimer-lens epithelium-derived M. Tsiang, GS Jones, M. Hung, S. Mukund, B. Han, X. Liu, K. Babaoglu, E. Lansdon, X. Chen, J. Todd, T. Cai, N. Pagratis, R. Sakowicz, R. Geleziunas J. Biol. Chem. (2009) 248, 33580-99 31. Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy Antiviral Research (2010) 85, 101-18 32. Susceptibility of Treatment-Naive HCV Clinical Isolates to HCV Protease Inhibitors Andrew Bae, Siu-Chi Sun, Xiaoping Qi, Xiaowu Chen, Karin Ku, Angela Worth, Kelly A. Wong, Jeanette Harris, Michael D. Miller and Hongmei Mo Antimicrobial Agents andChemotherapy (2010) 54:5288-97 33. Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease. Clarke MO, Chen X, Cho A, Delaney WE 4th, Doerffler E, Fardis M, Ji M, Mertzman M, Pakdaman R, Pyun HJ, Rowe T, Yang CY, Sheng XC, Kim CU. Bioorg Med Chem Lett. (2011) 21:3568-72 34. Conformationally Constrained Tricyclic HIV Integrase Inhibitors M. Fardis, H. Jin, X. Chen, M. Tsiang, J.M. Chen, C. Kim, M. Wright HIV-1 Integrase: Mechanism and Inhibitor Design (2010, N. Nemati, B. Wang eds.), Wiley, 35. Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease. Clarke MO, Byun D, Chen X, Doerffler E, Leavitt SA, Sheng XC, Yang CY, Kim CU. Bioorg Med Chem Lett. (2012) 22:1095-8 36. Discovery of GS-9256: a novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity Sheng XC, Casarez A, Cai R, Clarke MO, Chen X, Cho A, Delaney WE 4th, Doerffler E, Ji M, Mertzman M, Pakdaman R, Pyun HJ, Rowe T, Wu Q, Xu J, Kim CU. Bioorg Med Chem Lett. (2012) 22:1394-6 37. Discovery of GS-9451: an acid inhibitor of the hepatitis C virus NS3/4A protease Sheng XC, Appleby T, Butler T, Cai R, Chen X, Cho A, Clarke MO, Cottell J, Delaney WE 4th, Doerffler E, Link J, Ji M, Pakdaman R, Pyun HJ, Wu Q, Xu J, Kim CU. Bioorg Med Chem Lett. (2012) 22:2629-34

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