Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Dr. Xiaoyan Chen is a Professor and Principal Investigator in the Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Dr. Chen’s research interest focuses on the drug metabolism and pharmacokinetics. She has developed two systems for rapid metabolite identification employing high resolution MS strategies and for PK evaluation based on the LC/MS/MS techniques, which provide the technical and methodological supports for ADME research of innovative drugs. She established the first research group in China, focused on mechanisms of Metabolic Activation Induced Drug Adverse Effect. She has made significant progress in understanding the relationship between the formation of reactive metabolites and drug toxicities. Some findings showed that different pathological situations in patients (inflammation, oxidative stress or hepatic insufficiency), competing metabolic pathways (bioinactivation), co-administered drugs may alter the bioactivation extent and cause variable idiosyncratic toxicities. Focused on innovative drugs R&D, several novel biotransformation pathways were discovered，and their chemistry and biochemistry mechanisms were unraveled by establishing in vitro cellular models for drug absorption and metabolism. Dr. Chen has served as a principal investigator, conducting studies to evaluate preclinical and clinical ADME studies of new drug candidates. Among them, six innovative drugs have been approved by CFDA for marketing; more than 50 candidates have been approved to initiate human studies in China, 4 in USA. She has published 140 articles in international peer reviewed journals, which are cited more than 1500 and has co-edited three books. As the principle investigator, she has hold four projects supported by NSFC, and participated in the National Science and Technology Major Projects-Major New Drugs, the program of National “973” project and National Climb Plan, and the Key Program supported by NSFC.

EDUCATION

09/1990 - 07/1994,B.Sc. in Pharmacy,Shenyang Pharmaceutical University

08/1994 - 07/1999,Ph.D. in Pharmaceutical Analysis,Shenyang Pharmaceutical University

WORK EXPERIENCE

08/1999 - 10/2001,Shenyang Pharmaceutical University,Assistant Professor of Pharmacy

11/2001 - 09/2003,Shenyang Pharmaceutical University,Associate Professor of Pharmacy

10/2003 - 04/2005,Shenyang Pharmaceutical University,Professor of Pharmacy

05/2005 - present,Shanghai Institute of Materia Medica, Chinese Academy of Sciences,DMPK Center,Principal Investigator,Director of Bioanalysis Section

Research Directions

1.Research on the mechanisms of drug metabolism and transportation responsible for involved in the drug adverse reactions
2.Research on the chemical and biological mechanisms of uncommon drug metabolism pathways
3.Developing new bioanalytical methods for ADME studies
4.Constructing the platform for ADME investigations of new drug candidates

Grants & Research Projects

1.Natural Science Foundation of China The study on the metabolism and DDI of chlorogenic acid to elucidate the mechanism of adverse reaction of TCM injection,Project Leader,1/2012-12/2015
2.National “973” project and National Climb Plan supported by Ministry of Science and Technology,The study of the improvement of efficacy of poor solubility drug by nanotechnology,Core scientist,1/2009-12/2012
3.Natural Science Foundation of China,Investigation on bioactivation of bisbenzylisoquinoline drugs,Project Leader,1/2009-12/2011
4.National Science and Technology Major Projects-Major New Drugs,Comprehensive technique platform of drug research and development,Core scientist,1/2009-12/2010

Achievements

1.research on the mechanism of drug metabolism and transportation involved in drug adverse effects
2.Identification of metabolites and the mechanism of drug metabolism
3.Developing new bioanalytical methods for ADME studies
4.Construction of the platform for drug metabolism and pharmacokinetics studies

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Social Titles

The council member of China Mass Spectrometry Society

Shanghai Pharmaceutical Association,Vice director of Pharmaceutical Analysis Committee

Member Editor of Chinese Journal of Clinical Pharmacology and Therapeutics

VIP Member of Chinese Pharmaceutical Association

Member of Chinese Pharmacological Society

Member of the International Society for the Study of Xenobiotics

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Awards & Honors

2004,The second prize for scientific and technological progress of Liaoning Province

2003,The second prize for scientific and technological progress of Liaoning Province

2003,The first prize for scientific and technological progress of the city of Shenyang

2001,The first prize for CAIA Prize of China Association for instrumental Analysis

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Pubilcations

Full Publication List

Selected Publications

1.Zhong K, Li XL, Xie C, Zhang YF, Zhong DF, Chen XY*. Effects of renal impairment on the pharmacokinetics of morinidazole: uptake transporter-mediated renal clearance of the conjugated metabolites. Antimicrob Agents Chemother, 2014, doi:10.1128/AAC.02414-14

2.Diao XX, Pang XY, Xie C, Guo ZT, Zhong DF, Chen XY*. Bioactivation of 3-n-Butylphthalide (NBP) via Sulfation of Its Major Metabolite 3-Hydroxy-NBP: Mediated Mainly by Sulfotransferase 1A1. Drug Metab Dispos, 42: 774-81, 2014

3.Xie C, Zhong DF, Chen XY*. A fragmentation-based method for the differentiation of glutathione conjugates by high-resolution mass spectrometry with electrospray ionization. Anal Chim Acta, 788: 89-98, 2013

4.Deng P, Zhong DF, Yu K, Zhang YF, Wang T, Chen XY*. Pharmacokinetics, metabolism, and excretion of the antiviral drug arbidol in humans. Antimicrob Agents Chemother, 574: 1743-1755, 2013

5.Diao XX, Deng P, Xie C, Li XL, Zhong DF, Zhang YF, Chen XY*. Metabolism and pharmacokinetics of 3-n-butylphthalide (NBP) in humans: the role of cytochrome P450s and alcohol dehydrogenase in biotransformation. Drug Metab Dispos, 41: 430-444, 2013

6.Xie C, Zhou JL, Guo ZT, Diao XX, Gao ZW, Zhong DF, Jiang HY, Zhang LS, Chen XY*. Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Brit J Pharmacol, 168: 1687-1706, 2013

7.Chen MX, Liu K, Zhong DF, Chen XY*. Trimethylsilyldiazomethane derivatization coupled with solid-phase extraction for the determination of alendronate in human plasma by LC-MS/MS. Anal Bioanal Chem, 402: 791-798, 2012

8.Xie C, Zhong DF, Chen XY*. Identification of the ortho-benzoquinone intermediate of 5-O-caffeoylquinic acid in vitro and in vivo: Comparison of bioactivation under normal and pathological situations. Drug Metab Dispos, 40: 1628-1640, 2012

9.Gao RN, Li L, Xie C, Diao XX, Zhong DF, Chen XY*. Metabolism and pharmacokinetics of morinidazole in humans: Identification of diastereoisomeric morpholine N+-glucuronides catalyzed by UDP-glucuronosyl- transferase 1A9. Drug Metab Dispos, 40: 556-567, 2012

10.Jin H, Li L, Zhong DF, Liu J, Chen XY*, Jiang Zheng*. Pulmonary toxicity and metabolic activation of tetrandrine in CD-1 Mice. Chem Res Toxicol, 24, 2142-2152 , 2011

11.Deng P, Zhong DF, Nan FJ, Liu S, Li D, Yuan T, Chen XY*, Zheng J*. Evidence for the bioactivation of 4-nonyphenol to quinine methide and ortho-benzoquinone metabolites in human liver microsomes. Chem Res Toxicol, 23: 1617-1628, 2010

12.Wang YY, Zhong DF, Chen XY*, Zheng J*. Identification of quinone methide metabolites of dauricine in human liver microsomes and in rat bile. Chem Res Toxicol, 22: 824-834, 2009

13.Chen XY. Profiling and characterization of bioactive substances of herbal medicine and their metabolites using mass spectrometry. In: Handbook of Metabolic Pathways of Xenobiotics, edited by Lee PW, Aizawa H, Gan LL, Prakash C, Zhong DF. John Wiley & Sons, Ltd., Volume 2, 2014

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