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技術轉化中心

張志遠博士

北京生命科學研究所資深研究員，技術轉化中心主任

Zhiyuan Zhang, Ph.D.

Investigator and Director of Translational Research Center, NIBS, Beijing，China

Phone：86-10-80726688-8575

E-mail：zhangzhiyuan@nibs.ac.cn

技術轉化中心

NIBS是世界一流的生命科學研究機構，聚集眾多優秀的從事生命科學研究的科學家，他們致力于尋找導致疾病和生命進程的根源，其許多研究成果具有極大開發潛力用以作為研發新的藥物或作為疾病早期檢測的靶點。本中心的目標之一就是開發基礎科研成果的應用潛質。我們實驗室配以先進的儀器裝備，如400MHz Verian核磁共振儀、制備型Waters液質聯用儀、分析型Agilent高效液相色譜儀、傅立葉變換紅外光譜儀、旋光儀、CEM微波反應儀、和自動化高通量篩選工作站等，應用現代藥物研發的新技術、新手段和新理念（蛋白晶體結構、計算機輔助設計、組合化學及高通量篩選等技術）來實現自主研發新藥的目標。實驗室近期將專注于治療癌癥和糖尿病的小分子藥物研發。

新藥物的研發雖是一個漫長、昂貴的和艱辛的歷程，無數人的千辛萬苦常常是以失敗為結局，但這并不能阻擋有志之師頑強地追求他們美妙的夢想?解除患者痛苦、帶給病人希望、享受那成功摘冠的喜悅。這也是我們的追求和夢想。

Research Description

Although it is an arduous, expensive, and difficult task, accompanied by seemingly low success rates, the accomplishment of creating and successfully delivering a new drug is a sweet dream that attracts many scientists and companies that are willing to spend great deals of effort and money to achieve it. Our lab is a determined group of people with that certain dream.

NIBS is a world class research institute. Some research results found by our scientists at NIBS would be great potential targets for the development of new drugs. It is one of our many goals to evaluate and study the possibility of developing new drugs based on those targets, using the latest technology and tools such as Structure Based Drug Design (SBDD) and High Throughput Screening (HTS). Our lab will focus on developing small molecule drugs for cancer and diabetes treatments.

教育經歷：

Education

1996年	瑞典隆德大學化學及化工中心化學博士
	Ph.D. in Chemistry, Lund University, Center for Chemistry and Chemical Engineering, Sweden
1983年	天津南開大學化學系學士學位
	B.S. in Organic Chemistry, Department of Chemistry,Nankai University, Tianjin, China

工作經歷

Professional Experience

2011年-	北京生命科學研究所資深研究員，技術轉化中心主任
	Investigator and Director of Translational Research Center, National Institute of Biological Sciences, Beijing, China
2005-2010年	武田制藥，美國，首席科學家，從事抗癌新藥、抗代謝綜合癥和動脈粥樣硬化新藥以及抗高血壓新藥的研發
	Takeda San Diego, Principal Scientist, Worked on three therapeutic areas, oncology, metabolic disease and hypertension.
2002-2005年	美國斯拉克斯，資深科學家-首席科學家，從事抗癌新藥和抗糖尿病新藥的開發。是抗糖尿病上市新藥Alogliptin(Nesina®)的研發人，并研發出其他3個藥物分別進入I-III期臨床試驗。
	Syrrx, San Diego, Senior Scientist-Principal Scientist, Worked on two projects, anti diabetes target DPP4 and anti cancer target Aurora B kinase, delivered 4 clinical candidates that entered clinical trials and reached phase I to phase III individually, is the inventor of the new anti diabetes drug Alogliptin(Nesina®).
1999-2002年	美國歐迪美制藥，資深科學家，作為公司核心技術的創建人參與公司的早期組建，負責公司的新技術的研發。從事了抗癌疫苗及新抗菌素的研發。
	Optimer Pharmaceuticals, Senior Scientist, As an inventor of company’s core technology and founding scientist, led new technology development and their application; also involved in two drugs discovery projects, cancer vaccine development and new antibiotic research.
1996-2000年	美國斯普瑞斯研究所博士后，師從翁啟惠教授，研創多項多糖合成技術（例如計算機程序預選一鍋燴合成多糖技術），開發新的合成方法，以及完成多個癌細胞抗原的合成。
	Postdoctoral research with Professor Chi-Huey Wong，The Scripps Research Institute. Initiated and developed a few new technologies and methodologies for oligosaccharide synthesis such as programmable one-pot oligosaccharide synthesis and completed the total synthesis of many natural products, such as cancer antigens.
1990-1996年	瑞典隆德大學化學及化工中心博士論文指導教授 Goran Magnusson，從事合成脫氧Gb3衍生物-探索其于verotoxins 的結合方式
	Ph.D.dissertation research with Professor Goran Magnusson, synthesized monodeoxy neoglycolipid analogues of Gb3 and developed new methods in organic synthesis.

發表文章

Publications

1.	Z. Zhang, M. B. Wallace, J. Feng, J. A. Stafford, J.A. Skene, L. Shi, B. Li, K. Aertgeerts, A. Jennings, R. Xu, D. B. Kassel, S. W. Kaldor, M. Navre, D. R. Webb and S. L. Gwaltney, II.. “The Design and Synthesis of Pyrimidinone and Pyrimidinedione Inhibitors of Dipeptidyl Peptidase IV”, J. Med. Chem.2011 Jan 27;54(2):510-24.
2.	M. B. Wallace, J. Feng, Z. Zhang, R. J. Skene, L. Shi, C. L. Caster, D. B. Kassel, R. Xu and S. L. Gwaltney II.. “Structure-Based Design and Synthesis of Benzimidazole Derivatives as Dipeptidyl Peptidase IV Inhibitors” Bioorg. Med. Chem. Lett., 2008, 18, 2362-2367.
3.	J. Feng, Z. Zhang, M. B. Wallace, J. A. Stafford, S. W. Kaldor, D. B. Kassel, M. Navre, L. Shi, R. J. Skene, T. Asakawa, K. Takeuchi, R. Xu, D. R. Webb and S. L. Gwaltney, II.. “Discovery of Alogliptin: A Potent, Selective, Bioavailable, and Efficacious Inhibitor of Dipeptidyl Peptidase IV” J. Med. Chem., 2007, 50 (10), 2297-2300.
4.	Z. Zhang, K. Niikura, X.-F. Huang and C.-H. Wong. “A Strategy for the One-Pot Synthesis of Sialylated Oligosaccharides” Can. J. Chem., 2002, 80 (8), 1051.
5.	Z. Zhang and C.-H. Wong. “Regioselective Benzoylation of Sugars Mediated by Excessive Bu₂SnO: Observation of Temperature Promoted Migration” Tetrahedron, 2002, 58 (32), 6513-6519.
6.	F. Burkhart, Z. Zhang, S. Wacowich-Sgarbi and C.-H. Wong. “Synthesis of Globo H Using the Programmable Reactivity-Based One-Pot Strategy”Angew. Chem., Int. Ed. Engl., 2001, 40, 1274. Featured in C&EN News April 9, 2001. p. 49.
7.	Z. Zhang, I. R. Ollmann, X.-S.Ye, Ｒ. Wischnat, T. Baasov and C.-H. Wong. "Programmed One-Pot Synthesis of Oligosaccharides" J. Am. Chem. Soc.1999, 121, 734-753. Featured in Science, 1999, 283, 911 and in C&EN News Science/Technology March 22th, 1999.
8.	S. Vincent, M.D. Burkart, C.-Y. Tsai, Z. Zhang, and C.-H. Wong. "Electrophilic Fluorination-Nucleophilic Addition Reaction Mediated by Selectfluor: Mechanistic Studies and New Applications" J. Org. Chem.,1999, 64, 5264.
9.	S. Haataja, Z, Zhang, K. Tikkanen, G, Magnusson, and J. Finnne. “Determination of the Cell Adhesion Specificity of Streptococcus Suis with Complete Set of Monodeoxy Analogues of Globotriose" Glycoconjugate J.,1999, 16, 67.
10	C.-H. Wong, X.-S.Ye and Z. Zhang. "Assembly of Oligosaccharide Libraries Using A Designed Building Block and Efficient Orthogonal Protection-Deprotection Strategy" J. Am. Chem. Soc., 1998, 120, 7137. Featured inC&EN News Science/Technology, July. 20th, 1998, p. 49.
11	M. D. Burkart, Z. Zhang, S.-C. Hung and C.-H. Wong. "A New Method for the Synthesis of Fluoro-Carbohydrates and Glycosides Using Selectfluor"J. Am. Chem. Soc., 1997, 119, 11743. Featured in C&EN NewsScience/Technology Concentrates, Dec. 15th, 1997, p. 47.
12.	P.-G. Nyholm, G. Magnusson, Z. Zhang, R. Norel, Be. Binnington and C. A. Lingwood. "Two Distinct Bind Sites for Globotriosyl Ceramide on Verotoxins: Identification by Molecular Modeling and Confirmation Using Deoxy Analogues and a New Glycolipid Receptor for All Verotoxins" Chem & Biol 1996, 3, 263.
13.	Z. Zhang. "Synthesis of the Monodeoxy Neoglycolipid Analogues of Globotrioside; Development of Some New Methods in Carbohydrate Chemistry" Thesis, LUTKDH/(TKOK-1037)/1-82/(1996) 1996 Lund,Sweden.
14.	Z. Zhang and G. Magnusson. "DDQ-Mediated Oxidation of 4,6-O-Methoxybenzylidene-Formation of 4-OH, 6-Cl-, and 6-Br-derivatives" J. Org. Chem., 1996, 61, 2394-2400.
15.	Z. Zhang and G. Magnusson "Synthesis of Double-Chain Bis-Sulfone Neoglycolipids of the 2-, 3- and 6-Deoxyglobotrioses" J. Org. Chem., 1996, 61, 2383-2393.
16.	Z. Zhang and G. Magnusson. "Conversion of p-Methoxyphenyl Glycosides into the Corresponding Glycosyl Chlorides and Bromides, and into Thiophenyl Gycosides" Carbohydr. Res., 1996, 295, 41-55.
17.	Z. Zhang and G. Magnusson. "Synthesis of Double-Chain Bis-Sulfone Neoglycolipids of the 2’-, 3’- and 6’-Deoxyglobotrioses" J. Org. Chem., 1995, 60, 7304-7315.
18.	B. Boyd, G. Magnusson, Z. Zhang and C. A. Lingwood. "Lipid Modulation of Glyccolipid Receptor Function: Availability of Gal(a1-4)Gal Disaccharide for Verotoxin Bind in Nature and Synthetic Glycolipids" Eur. J. Biochem.,1994, 223, 873-878.
19.	Z. Zhang and G. Magnusson. "Synthesis of Double-Chain Bis-Sulfone Neoglycolipids of the 2''-, 3''-, 4''- and 6''-Deoxyglobotrioses" Carbohydr. Res., 1994, 262, 79-101.
20.	B. Boyd, G. Magnusson, A. Kiarash, Z. Zhang and C. A. Lingwood. "Lipid Modulation of Glycolipid Receptor Function: Presentation of Galactose a1-4 Galactose Disaccharide for Verotoxin Bind in Natural and Synthetic Glycolipids" Recent Advances in Verocytotoxin-producing E. Coli Infection,1994, 167.

著作章節

BOOKS AND CHAPTER

1. Z. Zhang and Chi-Huey Wong, "Glycosylation Method: Phosphite" Oligosaccharides in Chemistry and Biology: A Comprehensive Handbook: Synthesis of Oligosaccharides, Glycoconjugates and Glycomimetics; B. Ernst, G. Hart, P. Sina?, Eds.; Wiley-VCH, 2000, Vol. I, Part 1, Chapter 5.

專利

PATENTS

1.	Feng, J.; Gwaltney, S. L.; Lam, B.; Zhang, Z.; US 7825242 B2 published on 02-11-2010,
2.	Zhang, Z.; Elder, B.J.; Isbester, P. K.; Palmer, G.J.; Ulysse, L. G. “Dipeptidyl Peptidase Inhibitors.” US 7807689B2, published on 5-10-2010.
3.	Feng, J.; Gwaltney, S. L.; Stafford, J. A.; Zhang, Z.; Elder, B. J.; Isbester, P.K. Palmer, G.J.; Salsbury, J.S.; Ulysse, L.; “Dipeptidyl Peptidase Inhibitors.”US7795428B2, published on 14-09-2010.
4.	Cao, S. X; Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Stafford, J. A.; Wallace,M. B.; Xiao, X.-Y.; Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.”US7790734B2, published on 7-09-2010.
5.	Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Wallace, M. B.; Stafford, J. A.;Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7790736B2, published on7-09-2010.
6.	Feng, J.; Gwaltney, S. L.; Stafford, J. A.; Zhang, Z.; Elder, B. J.; Isbester, P.K. Palmer, G.J.; Salsbury, J.S.; Ulysse, L.; “Dipeptidyl Peptidase Inhibitors.”US7781584B2, published on 24-08-2010.
7.	Feng, J.; Gwaltney, S. L.; Wallace, M. B.; Stafford, J. A.; Zhang, Z.;“Dipeptidyl Peptidase Inhibitors.” US7723344B2, published on 25-05-2010.
8.	Dong, Q.; Hosfield, D. J.; Paraselli, B. R.; Scorah, N.; Stafford, J. A.; Wallace,M. B.; Zhang, Z.; “Kinase inhibitors” US7713973B2, published on 11-05-2010.
9.	Feng, J.; Gwaltney, S. L.; Wallace, M. B.; Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7687638B2, published on 30-03-2010.
10.	Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Stafford, J. A.; Wallace, M. B.;Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7687625B2, published on30-03-2010.
11.	Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Stafford, J. A.; Wallace, M. B.; Xiao, X.-Y.; Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7638638B2,published on 29-11-2009.
12.	Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Stafford, J. A.; Wallace, M. B.;Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7579357B2, published on25-08-2009.
13.	Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Stafford, J. A.; Wallace, M. B.;Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7550590B2, published on23-06-2009.
14.	Feng, J.; Gwaltney, S. L.; Kaldor, S. W.; Stafford, J. A.; Wallace, M. B.;Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US7470700B2, published on08-11-2009.
15.	Wong, C.-H.; Zhang, Z.; Ollmann, I.; Baasov, T.; Ye, X.-S. “ programmable One-Pot oligosaccharide synthesis” US7019131B2 published on 28-03-2006.
16.	Dong, Q.; Hosfield, D. J.; Paraselli, B. R.; Scorah, N.; Stafford, J. A.; Wallace,M. B.; Zhang, Z.; “Kinase inhibitors” US 2010/0216765 A1 published on26-Aug-2010.
17.	Kwok, L.; Lam, B.; Li, Z.; Zhang, Z.; “Renin inhibitors”US2010/0105665A1, published on 29-04-2010.
18.	Gwaltney, S. L.; Lam, B.; Zhang, Z. “Renin inhibitors” US2010/0137310A1 published on 03-06-2010.
19.	Bressi, J. C.; Chu, S.; Erickson, P.; Komandla, M.; Kwok, L.; Lawson, J. D.;Stafford, J. A.; Wallace, M. B.; Zhang, Z.; Das, S. “c-Met inhibitors” US 2010/0063054 A1 published on 11-03-2010
20.	Feng, J.; Gwaltney, S. L.; Stafford, J. A.; Zhang, Z.; Brodluahrer, P. R.;Elder, B.; Isbester, P.; Fornicola, R. S.; Kisanga, P. B.; Mobele, B. I.; Palmer, G. J.; Reeve, M. M.; Salsbury, J. S.; Ulysse, L.; Venkatraman, S. “Dipeptidyl Peptidase Inhibitors.” US 2009/0275750A1 published on 05-11-2009.
21.	Feng, J.; Gwaltney, S. L.; Wallace, M. B.; Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US 2007/0249611 A1, published on 25-10-2007.
22.	Feng, J.; Gwaltney, S. L.; Stafford, J. A.; Wallace, M. B.; Zhang, Z.;“Dipeptidyl Peptidase Inhibitors.” US 2006/0135767 A1, published on22-06-2006.
23.	Feng, J.; Gwaltney, S. L.; Wallace, M. B.; Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US20050272765A1, published on 08-11-2005.
24.	Feng, J.; Gwaltney, S. L.; Stafford, J. A.; Zhang, Z.; “Dipeptidyl Peptidase Inhibitors.” US 2005/0065144 A1, published on 24-03-2005.

榮譽&獎勵

Honors and Awards

1. Takeda Global Award 2008, Japan.

2. Structure-Based Drug Design Award 2004, Syrrx.

3. Scholarship from Swedish Natural Science Research Council.

4. Student travel award, Lund University, Sweden, 1992

5. Research publications were featured many times on C&EN News and Science.

· Featured in C&EN News April 19, 2001， p. 49

· Featured in Science, 1999, 283, 911

· Featured in C&EN News Science/Technology March 22th, 1999，p.30

· Featured in C&EN News Science/Technology, July. 20th, 1998, p. 49.

· Featured in C&EN News Science/Technology Concentrates, Dec. 15th, 1997, p. 47.