技术转化中心 - 科学研究 - 北京科学生命dcbox小金库(中国)

技术转化中心

张志远博士

北京科学生命dcbox小金库(中国)资深研究员，技术转化中心主任

Zhiyuan Zhang, Ph.D.

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

Phone：86-10-80726688-8575

E-mail：zhangzhiyuan@nmamn.com

技术转化中心

NIBS是世界一流的生命科学研究机构，聚集众多优秀的从事生命科学研究的科学家，他们致力于寻找导致疾病和生命进程的根源，其许多研究成果具有极大开发潜力用以作为研发新的药物或作为疾病早期检测的靶点。本中心的目标之一就是开发基础科研成果的应用潜质。我们实验室配以先进的仪器装备，如400MHz Verian核磁共振仪、制备型Waters液质联用仪、分析型Agilent高效液相色谱仪、傅立叶变换红外光谱仪、旋光仪、CEM微波反应仪、和自动化高通量筛选工作站等，应用现代药物研发的新技术、新手段和新理念（蛋白晶体结构、计算机辅助设计、组合化学及高通量筛选等技术）来实现自主研发新药的目标。实验室近期将专注于治疗癌症和糖尿病的小分子药物研发。

新药物的研发虽是一个漫长、昂贵的和艰辛的历程，无数人的千辛万苦常常是以失败为结局，但这并不能阻挡有志之师顽强地追求他们美妙的梦想−解除患者痛苦、带给病人希望、享受那成功摘冠的喜悦。这也是我们的追求和梦想。

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.

教育经历：

Education

1996年	瑞典隆德大学化学及化工中心化学博士
	Ph.D. in Chemistry, Lund University, Center for Chemistry and Chemical Engineering, Sweden
1983年	天津南开大学化学系学士学位
	B.S. in Organic Chemistry, Department of Chemistry,Nankai University, Tianjin, China

工作经历

Professional Experience

2011年-	北京生命科学研究所资深研究员，技术转化中心主任
	Investigator and Director of Translational Research Center, National Institute of Biological Sciences, Beijing, China
2005-2010年	武田制药，美国，首席科学家，从事抗癌新药、抗代谢综合症和动脉粥样硬化新药以及抗高血压新药的研发
	Takeda San Diego, Principal Scientist, Worked on three therapeutic areas, oncology, metabolic disease and hypertension.
2002-2005年	美国斯拉克斯，资深科学家-首席科学家，从事抗癌新药和抗糖尿病新药的开发。是抗糖尿病上市新药Alogliptin(Nesina®)的研发人，并研发出其他3个药物分别进入I-III期临床试验。
	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	美国欧迪美制药，资深科学家，作为公司核心技术的创建人参与公司的早期组建，负责公司的新技术的研发。从事了抗癌疫苗及新抗菌素的研发。
	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	美国斯普瑞斯研究所博士后，师从翁启惠教授，研创多项多糖合成技术（例如计算机程序预选一锅烩合成多糖技术），开发新的合成方法，以及完成多个癌细胞抗原的合成。
	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	瑞典隆德大学化学及化工中心博士论文指导教授 Goran Magnusson，从事合成脱氧Gb3衍生物-探索其于verotoxins 的结合方式
	Ph.D.dissertation research with Professor Goran Magnusson, synthesized monodeoxy neoglycolipid analogues of Gb3 and developed new methods in organic synthesis.

发表文章

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 dcbox小金库(中国) 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.

著作章节

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. Sinaÿ, Eds.; Wiley-VCH, 2000, Vol. I, Part 1, Chapter 5.

专利

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.

荣誉&奖励

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.