张洪建

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姓  名:张洪建

职称职务:特聘教授/博导

联系电话:65882659

电子邮箱:zhanghongjian@suda.edu.cn

办公地址:云轩楼1132

 

 

个人简介:

一、学习工作经历

1、学历背景:

1979.91983.7  北京师范大学化学系 大学本科

1988.81991.7  加州大学-戴维斯 食品化学硕士生

1991.81994.9  加州大学-戴维斯 农业/环境化学博士生, Ph.D

2、国外学习研究经历:

1994.101999.3 美国国家健康研究中心(NIH) 博士后研究员

1999.42007.12 美国施贵宝(Bristol-Myers Squibb)新药研发中心    成药性研究(药物代谢动力学、制剂、安全性评估等)课题组长

3、工作经历:

1983.81988.7  山东农业大学化学系 助教/讲师

1999.42007.12 美国施贵宝(Bristol-Myers Squibb)新药研发中心 首席科学家/课题组长

2008.12011.7 美国PharmaResources Inc. 药物代谢主管

2011.8        苏州大学医学部药学院 教授/博导

 

二、研究方向

1)代谢反应类型鉴定、代谢酶基因亚型对清除率的影响

2)药物转运体在ADME过程中的作用

3)由代谢酶及转运体介导的药物相互作用

 

三、主要研究成果

完成12项临床前药物代谢动力学评估及研究工作,发表学术论文46篇,其中SCI收录论文40多篇。

1、论文*表示为通讯作者

学术专著章节:

1.  Zhang H, Sinz MW and Rodrigues AD. (2007) Metabolism-mediated drug-drug interactions (book chapter) in Drug Metabolism in Drug Design and Development: Basic Concepts and Practice. Wiley, New York.

2.  German JB, Zhang H, and Berger R. (1992) Role of lipoxygenases in lipid oxidation in foods. ACS Symposium Series-American Chemical Society publications (pubs.acs.org).

 

邀请综述:

3.  Fowler S. and Zhang H. (2008) In vitro evaluation of cytochrome P450 inhibition: current status on methodologies and their utility for predicting drug-drug interactions. AAPS J. 10(2):410-24.

4.  Zhang H, Davis C, Sinz M, and Rodrigues AD. (2007) Cytochrome P450 reaction phenotyping: an industrial perspective. Expert Opin Drug Metab Toxicol. 3(5):667-87.

5.  Zhang H, Cui D, Wang B, Han YH, Balimane P, Yang Z, Sinz M, Rodrigues AD. (2007) Pharmacokinetic drug interactions involving 17alpha-ethinylestradiol : a new look at an old drug. Clin Pharmacokinet. 46(2): 133-57.

 

学术论文:

6.  Dyckman AJ, Li T, Pitt S, Zhang R, Shen DR, McIntyre KW, Gillooly KM, Shuster DJ, Doweyko AM, Sack JS, Kish K, Kiefer SE, Newitt JA, Zhang H, Marathe PH, McKinnon M, Barrish JC, Dodd JH, Schieven GL, Leftheris K.(2011) Discovery of pyrrolo[2,1-f][1,2,4]triazine C6-ketones as potent, orally active p38α MAP kinase inhibitors. Bioorg Med Chem Lett. 21(15):4633-7.

7.  Fancher RM, Zhang H, Sleczka B, Derbin G, Rockar R, Marathe P (2011) Development of a canine model to enable the preclinical assessment of ph-dependent absorption of test compounds. J Pharm Sci. 100(7):2979-88.

8.  Gan J, Chen W, Shen H, Gao L, Hong Y, Tian Y, Li W, Zhang Y, Tang Y, Zhang H, Humphreys WG, Rodrigues AD. (2010) Repaglinide-Gemfibrozil Drug Interaction: Inhibition of Repaglinide Glucuronidation as a Potential Additional Contributing Mechanism. Br J Clin Pharmacol. 70(6):870-80.

9.  Fink BE, Norris D, Mastalerz H, Chen P, Goyal B, Zhao Y, Kim SH, Vite GD, Lee FY, Zhang H, Oppenheimer S, Tokarski JS, Wong TW, Gavai AV. (2010) Novel pyrrolo[2,1-f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases. Bioorg Med Chem Lett. [Epub ahead of print]

10. Das J, Moquin RV, Dyckman AJ, Li T, Pitt S, Zhang R, Shen DR, McIntyre KW, Gillooly K, Doweyko AM, Newitt JA, Sack JS, Zhang H, Kiefer SE, Kish K, McKinnon M, Barrish JC, Dodd JH, Schieven GL, Leftheris K. (2010) 5-amino-pyrazoles as potent and selective p38α inhibitors. Bioorg Med Chem Lett. 2010 Dec 1;20(23):6886-9.

11. Liu C, Lin J, Wrobleski ST, Lin S, Hynes J, Wu H, Dyckman AJ, Li T, Wityak J, Gillooly KM, Pitt S, Shen DR, Zhang RF, McIntyre KW, Salter-Cid L, Shuster DJ, Zhang H, Marathe PH, Doweyko AM, Sack JS, Kiefer SE, Kish KF, Newitt JA, McKinnon M, Dodd JH, Barrish JC, Schieven GL, Leftheris K. (2010) Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N- propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases. J Med Chem. 23;53 (18):6629-39.

12. Marathe P, Tang Y, Sleczka B, Rodrigues AD, Gavai A, Wong T, and Zhang H. (2010) Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 99(8): 3579-93.

13. Chang SY, Fancher RM, Zhang H, and Gan J. (2010) Mechanism-based inhibition of human cytochrome P4503A4 by domperidone. Xenobiotica. 40(2): 138-145.

14. Gavai AV, Fink BE, Fairfax DJ, Martin GS, Rossiter LM, Holst CL, Kim SH, Leavitt KJ, Mastalerz H, Han WC, Norris D, Goyal B, Swaminathan S, Patel B, Mathur A, Vyas DM, Tokarski JS, Yu C, Oppenheimer S, Zhang H, Marathe P, Fargnoli J, Lee FY, Wong TW, Vite GD. (2009) Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol- 5-ylamino]-5-methylpyrrolo[2,1-f] [1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epidermal growth factor receptor 1 and 2 kinases. J Med Chem. 12;52(21):6527-30.

15. Chang SY, Li W, Traeger SC, Wang B, Cui D, Zhang H, Wen B, Rodrigues AD. (2008) Confirmation that cytochrome P450 2C8 (CYP2C8) plays a minor role in (S)-(+)-and (R)-(-)-ibuprofen hydroxylation in vitro. Drug Metab Dispos. 36(12):2513-22.

16. Li J, Chen SY, Murphy BJ, Flynn N, Seethala R, Slusarchyk D, Yan M, Sleph P, Zhang H, Humphreys WG, Ewing WR, Robl JA, Gordon D, Tino JA. (2008) (D)-2-tert-Butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid: synthesis and incorporation into the growth hormone secretagogues. Bioorg Med Chem Lett. 18(14):4072-4.

17. Das J, Moquin RV, Pitt S, Zhang R, Shen DR, McIntyre KW, Gillooly K, Doweyko AM, Sack JS, Zhang H, Kiefer SE, Kish K, McKinnon M, Barrish JC, Dodd JH, Schieven GL, Leftheris K. (2008) Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors. Bioorg Med Chem Lett. 18(8):2652-7.

18. Hynes J Jr, Wu H, Pitt S, Shen DR, Zhang R, Schieven GL, Gillooly KM, Shuster DJ, Taylor TL, Yang X, McIntyre KW, McKinnon M, Zhang H, Marathe PH, Doweyko AM, Kish K, Kiefer SE, Sack JS, Newitt JA, Barrish JC, Dodd J, Leftheris K. (2008) The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38alpha MAP kinase inhibitor. Bioorg Med Chem Lett. 18(6):1762-7.

19. Liu C, Lin J, Pitt S, Zhang RF, Sack JS, Kiefer SE, Kish K, Doweyko AM, Zhang H, Marathe PH, Trzaskos J, McKinnon M, Dodd JH, Barrish JC, Schieven GL, Leftheris K. (2008) Benzothiazole based inhibitors of p38alpha MAP kinase. Bioorg Med Chem Lett. 18(6):1874-9.

20. Li J, Chen SY, Tao S, Wang H, Li JJ, Swartz S, Musial C, Hernandez AA, Flynn N, Murphy BJ, Beehler B, Dickinson KE, Giupponi L, Grover G, Seethala R, Sleph P, Slusarchyk D, Yan M, Humphreys WG, Zhang H, Ewing WR, Robl JA, Gordon D, Tino JA. (2008) Design and synthesis of tetrazole-based growth hormone secretagogue: The SAR studies of the O-benzyl serine side chain. Bioorg Med Chem Lett. 18(6):1825-9.

21. Hynes J Jr, Dyckman AJ, Lin S, Wrobleski ST, Wu H, Gillooly KM, Kanner SB, Lonial H, Loo D, McIntyre KW, Pitt S, Shen DR, Shuster DJ, Yang X, Zhang R, Behnia K, Zhang H, Marathe PH, Doweyko AM, Tokarski JS, Sack JS, Pokross M, Kiefer SE, Newitt JA, Barrish JC, Dodd J, Schieven GL, Leftheris K. (2008) Design, Synthesis, and Anti-inflammatory Properties of Orally Active 4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazine p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 51(1):4-16.

22. Li J, Chen SY, Li JJ, Wang H, Hernandez AS, Tao S, Musial CM, Qu F, Swartz S, Chao ST, Flynn N, Murphy BJ, Slusarchyk DA, Seethala R, Yan M, Sleph P, Grover G, Smith MA, Beehler B, Giupponi L, Dickinson KE, Zhang H, Humphreys WG, Patel BP, Schwinden M, Stouch T, Cheng PT, Biller SA, Ewing WR, Gordon D, Robl JA, Tino JA. (2007) Discovery of a tetrazole-based growth hormone secretagogue: 4-(hydroxybutyl)carbamic acid 2-{5-[1-(2-amino-2-methylpropionylamino)-2- benzyloxyethyl]tetrazol-1-yl}ethyl ester (BMS-317180). J Med Chem. 50(24):5890-3.

23. Zhang D, Zhang D, Cui D, Gambardella J, Ma L, Barros A, Wang L, Fu Y, Rahematpura S, Nielsen J, Zhang H, Humphreys WG. (2007) Characterization of the UGT activity of human liver microsomes genotyped for the UGT1A1*28 polymorphism. Drug Metab Dispos. 35(12):2270-80.

24. Vuppugalla V, Chang S-Y, Zhang H, Marathe P, and Rodrigues AD. (2007) Effects of commonly used organic solvents on the kinetics of cytochrome P450 2B6- and 2C8-dependent activities in human liver microsomes. Drug Metab Dispos. 35(11):1990-5.

25. Mastalerz H, Chang M, Chen P, Fink BE, Gavai A, Han WC, Johnson W, Langley D, Lee FY, Leavitt K, Marathe P, Norris D, Oppenheimer S, Sleczka B, Tarrant J, Tokarski JS, Vite GD, Vyas DM, Wong H, Wong TW, Zhang H, Zhang G. (2007) 5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Bioorg Med Chem Lett. 17(17):4947-54. 

26. Yao M, Zhu M, Sinz M, Zhang H, Humphreys W, Rodrigues A, Dai R. (2007) Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysis. J Pharm Biomed Anal. 44(1):211-23.

27. Mastalerz H, Chang M, Gavai A, Johnson W, Langley D, Lee FY, Marathe P, Mathur A, Oppenheimer S, Tarrant J, Tokarski JS, Vite GD, Vyas DM, Wong H, Wong TW, Zhang H, Zhang G. (2007) Novel C-5 aminomethyl pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Bioorg Med Chem Lett. 17(10):2828-33. 

28. Zhang H, Zhang D, Li W, Yao M, Darienzo C, Li YX, Ewing WR, Gu Z, Zhu Y, Murugesan N, Shyu WC, Humphreys WG. (2007) Reduction of site-specific CYP3A-mediated metabolism for dual angiotensin II and endothelin antagonists in various in vitro systems and cynomolgus monkeys. Drug Metab Dispos. 35(5):795-805.

29. Mastalerz H, Chang M, Chen P, Dextraze P, Fink BE, Gavai A, Goyal B, Han WC, Johnson W, Langley D, Lee FY, Marathe P, Mathur A, Oppenheimer S, Ruediger E, Tarrant J, Tokarski JS, Vite GD, Vyas DM, Wong H, Wong TW, Zhang H, Zhang G. (2007) New C-5 substituted pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Bioorg Med Chem Lett. 17(7):2036-42.

30. Zhang D, Wang L, Chandrasena G, Ma L, Zhu M, Zhang H, Davis CD, Humphreys WG. (2007) Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar. Drug Metab Dispos. 35(1):139-49.

31. Wong TW, Lee FY, Yu C, Luo FR, Oppenheimer S, Zhang H, Smykla RA, Mastalerz H, Fink BE, Hunt JT, Gavai AV, Vite GD. (2006) Preclinical antitumor activity of BMS-599626, a pan-HER kinase inhibitor that inhibits HER1/HER2 homodimer and heterodimer signaling. Clin Cancer Res. 12(20 Pt 1):6186-93.

32. Das J, Furch JA, Liu C, Moquin RV, Lin J, Spergel SH, McIntyre KW, Shuster DJ, O'Day KD, Penhallow B, Hung CY, Doweyko AM, Kamath A, Zhang H, Marathe P, Kanner SB, Lin TA, Dodd JH, Barrish JC, Wityak J. (2006) Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors. Bioorg Med Chem Lett. 16(14):3706-12.

33. Liu C, Wrobleski ST, Lin J, Ahmed G, Metzger A, Wityak J, Gillooly KM, Shuster DJ, McIntyre KW, Pitt S, Shen DR, Zhang RF, Zhang H, Doweyko AM, Diller D, Henderson I, Barrish JC, Dodd JH, Schieven GL, Leftheris K. (2005) 5-Cyanopyrimidine derivatives as a novel class of potent, selective, and orally active inhibitors of p38alpha MAP kinase. J Med Chem. 48(20):6261-70.

34. Lin TA., McIntye K.W., Das J., Liu C., ODay K.D., Penhallow B., Hung C.Y., Whitney G.S., Shuster D.J., Yang X., Townsend R., Postelnek J., Lin J., Furch J.A., Kamath A.V., Zhang H., Marathe P.H., Perez-Villar J.J., Doweyko A., Killar L., Dodd J.H., Barrish J.C., Wityak J., Kanner S.B. (2004) Selective Itk inhibitors block T-cell activation and murine lung inflammation. Biochemistry. 43(34): 11056-62. 

35. Zhang H., Yao M., Morrison R.A., Chong S. (2003) Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats.  Arch Pharm Res. 26(9):768-72.

36. Yao M., Zhang H., Zhu M., Chong S., Morrison R.A. (2003) A rapid and sensitive LC/MS/MS assay for  quantitative determination of digoxin in rat plasma. J Pharm Biomed Anal. 32(6):1189-97.

37. Fura A., Harper T.M., Zhang H., Fung L., Shyu W.C. (2003) Shift in pH of biological fluids during storage and processing: effect on bioanalysis. J Pharm Biomed Anal. 32(3):513-22.

38. Trost S. U., Swanson, E., Gloss, B., Wang-Iverson, D. B., Zhang H., Volodarsky, T., Grover, G. J.,  Baxter, J. D., Chiellini, G., Scanlan, T. S., Dillman, W. H. (2000) The thyroid hormone receptor--selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Endocrinology 141: 3057-3064.

39. Li B, Zhang H Akbar M., and Kim H. Y. (2000) Negative regulation of cytosolic phospholipase A2 by melatonin in the rat pineal gland. Biochem. J. 351, 709-716.

40. Kim YS., Zhang H, and Kim HY. (2000) Profiling neurosteroids in cerebrospinal fluids and plasma  by gas chromatography/electron capturing negative chemical ionization mass spectrometry. Ana. Biochem. 277, 187-195.

41. Zhang H, Akbar M., and Kim HY. (1999) Melatonin: an endogenous negative modulator for 12-lipoxygenation in the rat pineal gland.  Biochem. J. 344, 487-493.

42. Kim H. Y., Edsall L., Garcia M., and Zhang H. (1999) The release of polyunsaturated fatty acids and their lipoxygenation in brain. Adv. Exp. Med. Biol. 447, 75-85. 

43. Zhang H, Hamilton JH., Salem N. Jr., and Kim HY. (1998) N-3 fatty acid deficiency in the rat pineal gland: effects on phospholipid molecular species composition and endogenous levels of melatonin and lipoxygenase products. J. Lipid Res. 39, 1397-1403.

 

44. Golub MS., Kaaekuahiwi MS., Eisele PH., Zhang H, Jones AD., and Eisele JH. (1998) Newborn tissue concentrations of bupivacaine following maternal epidural administration during labor. Boil. Neonate  74, 304-313.

45. Zhang H and German, JB. (1996) Dietary modulation of phospholipid fatty acid composition and  lipoxygenase products in mouse lung homogenates. Lipids, 31, 19-25.

46. Kuo JM, Pan BS, Zhang H, and German JB. (1994) Identification of 12-lipoxygenase in the hemolymph of tiger shrimp (Penaeus japonicus Bate). J Agric. Food Chem. 42, 1620-1623.

 

四、主要荣誉

Bristol-Myers Squibb(施贵宝)工作不到九年的时间内,带领并参与了多个新药研发课题组,共发现/开发15个候选药并进入了临床前、临床III期实验。由于出色的成果及贡献,多次获得Bristol-Myers Squibb公司颁发的“明星员工奖”

 

五、社会兼职

中国药理协会药物代谢动力学专业委员会理事