Translational Research Center

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Scientists&Research

Translational Research Center

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

Translational Research Center

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.

Education

1996	Ph.D. in Chemistry, Lund University, Center for Chemistry and Chemical Engineering, Sweden
1983	B.S. in Organic Chemistry, Department of Chemistry,Nankai University, Tianjin, China

Professional Experience

2011-	Investigator and Director of Translational Research Center, National Institute of Biological Sciences, Beijing, China
2005-2010	Takeda San Diego, Principal Scientist, Worked on three therapeutic areas, oncology, metabolic disease and hypertension.
2002-2005	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	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	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	Ph.D.dissertation research with Professor Goran Magnusson, synthesized monodeoxy neoglycolipid analogues of Gb3 and developed new methods in organic synthesis.

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.

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.

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.

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.