暨南大学新药研究所简介

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暨南大学 /2011-07-21

暨南大学新药研究所简介

暨南大学新药研究所成立于2005年。经过几年的建设与发展，新药研究所已初具规模，现有教授2名，副教授2名，具有博士学位者5名，其他人员及博士硕士研究生20余名。

新药研究所承担学院的教学和科研工作。在新药的研究与开发方面，主要从事新靶点药物与中药有效成分的化学结构修饰，药理活性和作用机理研究，旨在获得疗效更高、毒性更低的具有自主知识产权的全新药物。目前的主要研究领域包括抗肿瘤药物、抗感染药物、心脑血管系统药物、治疗老年痴呆症及糖尿病药物等。

一、主要人员介绍

所长：王玉强，教授, 1987年获美国 The University of Texas Health Science Center at Houston and M. D. Anderson Cancer Center博士学位 (药物化学)。随后进入美国耶鲁大学 (Yale) 医学院药理系和加拿大阿尔伯特大学 (The University of Alberta) 化学系做博士后研究。九十年代初进入美国加州硅谷的生物医药公司从事药物的研究与开发工作，2005年回国到暨南大学工作, 现任暨南大学教授，药学院院长，博士生导师。

副所长：于沛, 研究员，1997年获香港中文大学博士学位 (有机化学), 其导师为香港中文大学新亚书院院长, 中国科学院院士Henry C. Wong (黄乃正)教授。后赴英国诺丁汉大学师从国际著名科学家、英国皇家科学院士G. Pattenden教授从事抗肿瘤天然产物的全合成研究，2000年回国任广州白云山制药股份有限公司技术中心副主任、白云山化学制药厂研究所所长，负责组建了广州市重点技术工程中心及白云山化学药创新中心。于沛博士具有丰富的抗感染药物研究开发经验，组织并主持了国家、省、市政府科技攻关计划十多项，成功开发产业化项目多项，创造了可观的经济效益。2007年初加入暨南大学药学院，从事药学教育与创新药物的研究。

蒋杰: 副教授，1998年毕业于同济医科大学药学院药物化学专业获硕士学位，2004年获得华中科技大学同济医学院药理学博士学位 (药理学)。1998年至2005年在三九集团主要从事新药开发，历任三九医药开发部助理研究员、研究主管、三九医药股份有限公司国际新药办主任、三九集团国家级技术中心海外新药部部长兼生物工程研究室主任。2006年3月调入暨南大学药学院，目前主要从事新药研究与开发及教学工作。

徐立朋: 副教授，2006年7月获中山大学中山医学院药理学博士学位，同年9月赴美国伊利诺伊大学（University of Illinois）进行博士后研究，主要通过细胞和动物模型进行肿瘤免疫方面的研究。2008年7月回国进入暨南大学药学院工作，从事创新药物的研发与药理学研究及教学工作。

教师：肖瑛、张在军、张高小

博士研究生：江晓间、徐俊、孙业伟

硕士研究生：

2007级：王中利、孙红莉、许长林、陈永红、曾祥萍、卢肖宇、陈海南、巫剑锋

2008级：刘伟、易鹏、崔庆彬、刘铭、李威、张名娟、杜静、李珍珠、万赛男、王磊

二、科研情况介绍

1. 抗肿瘤药物

DNA minor groove-binding anticancer drugs. CC-1065, a natural product, is one of the most potent anticancer drugs ever discovered. It selectively binds to the AT-rich sequence in the DNA minor groove, and alkylates DNA to cause DNA breaks, leading to cancer cell death. Over the last 20 years, we have synthesized many CC-1065 analogs and study their structure-activity relationship. YW-391 is our latest discovery, which reacts with albumin in the blood forming a conjugate. The latter is selectively taken up by cancer cells, leading to a higher therapeutic efficacy. YW-391 is currently under preclinical evaluation.

Topoisomerase Inhibitors. Camptothecins is a relatively new class of anticancer drugs. Over the last several years, we have synthesized tumor-targeted new camptothecin derivatives. One of such compounds is DHA-HCPT, which is a conjugate of 10-hydroxycamptothecin and DHA. DHA-HCPT is selectively accumulated by tumor, and for this reason, DHA-HCPT has a high therapeutic efficacy than its free drug 10-hydroxycamptothecin.

2. 心脑系统药物

The improving economic standard makes people live longer and healthier. Unfortunately, the aging population also suffers more cardio- and cerebro- vascular diseases. Professor Wang Yuqiang and his US team had previously successfully developed a blockbuster Alzheimer’s drug memantine. Now, we are working on new drugs based on traditional Chinese medicine for the treatment of cardio- and cerebro- vascular diseases. Such traditional Chinese medicine includes 丹参 and 川芎。

丹参素川芎嗪

3. 抗感染药物

Infectious diseases prove to be tough to eradicate and remain to be a major threat to human health. Deadly new species such as HIV, SARS and bird flu viruses continue to appear. Thus, finding new and effective anti-infectious disease treatment is an urgent task. We have been pursuing research in this area based on traditional Chinese medicine such as 穿心莲

穿心莲内酯

三、科研成果

新药所骨干人员近年发表主要论文：

. We have synthesized new compounds and found them to have novel biological properties. Our clinical candidate is currently under formal pre-clinical studies.

1、Wang, X.; Wang, Y.; Zheng, C. Isolation and purification of honokiol and magnolol from Cortex Magnoliae Officinalis by high-speed counter-current chromatography. J. ChromatographyA., 1036, 171, 2004.

2、Wang, X.; Wang, Y.; Yuan, J.; Sun, Q.; Liu, J.; Zheng, C. An efficient new method for extraction, separation and purification of psoralen and isopsoralen from Fructus Psoraleae by supercritical fluid extraction and high-speed counter-current chromatography. J. ChromatographyA, 1055, 135, 2004.

3、Jiang, J.; Li, S.; Li, M.; Xiang, J. Antiviral effect of chinonin against herpes simplex virus. J. Hua Zhong University of Science and technology (Health Sciences, English Version), 24, 521-524,2004.

4、Wang, Y.; Li, L.; Jiang, W.; Larrick, J. W. Synthesis and evaluation of a DHA and 10-hydroxcamptothecin conjugate. Bioorg. Med. Chem. 13, 5592–5599, 2005.

5、Wang, Y.; Li, L.; Jiang, W.; Yang, Z.; Zhang, Z. Synthesis and preliminary antitumor activity evaluation of a DHA and doxorubicin conjugate. Bioorg. Med. Chem. Lett. 16，2974-2977，2006.

6、Wang, Y.; Li, L.; Tian, Z.; Jiang, W.; Larrick, J. W. Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 14, 7854-7861,2006.

7、Wang, Y.; Eu, J.; Washburn, M.; Gong, T.; Chen, H. S. V.; Larrick, J. W.; Lipton, S. A.; Stamler, J, S.; Went, G. T.; Porter, S. The Pharmacology of Aminoadamantane nitrates. Curr. Alzheimer Res. 3, 201-204, 2006.

8、Xu, L.P.; Jiang, W. J.; Ma, T.; Qiu, P. X.; Hou, J.; Huang, Y. J.; Chen, J. S.; Yan, G, M. Expression, purification and molecular modeling of recombinant fibrinogenase Ⅳ, a metalloproteinase from Deinakistrodon acutus venom. Toxicon. 47, 241-248, 2006.

9、Xu, L. P.; Ma, T.; Jiang, W J.; Qiu, P. X.; Wang, X.; Su, X. W.; Yan, G. M. Recombinant production of fibrinogenase IV from Agkistrodon acutus venom and its preliminary evaluation.Appl Microbiol Biotechnol. 72, 72-76, 2006.

10、Yang, Z. Q. Synthesis and in vitro biological activity evaluation of the derivatives of Combretastatin A-4. Lett. Drug Des. Discovery, 3, 544-546, 2006.

11、Yang, Z. Q. Microwave-Assisted Rapid Synthesis of Intermediate of Ezetimibe. Chemical Journal on Internet, 8, 37, 2006.

12、Yang, Z. Q.; Sun, P. 3D-QSAR study of Potent Inhibitor of Phosphodiesterase-4 by using CoMFA approach. Int. J. Mol. Sci., 8, 714-722, 2007.

13、Wang, Y., Yang, Z.; Wright, S. C.; Larrick, J. W. Synthesis and preliminary antitumor activity of distamycin nitrogen mustards. Lett. Drug Design and Discov. 4, 37-39, 2007.

14、Suo, X. B.; Zhang, H.; Wang, Y. HPLC determination of andrographolide in rat whole blood: study on the pharmacokinetics of andrographolide incorporated in liposomes and tablets. Biomed Chromatogr. 21, 730-734, 2007.

15、Suo Xubin, Deng Yingjie, Zhang Han, Wang Yuqiang. Degradation kinetics of water-insoluble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes.Arch Pharm Res. 30, 876-883, 2007.

16、 Wang, Y.; Jiang, J.; Jiang, X.; Cai, S.; Han, H.; Li, L.; Tian, T.; Jiang, W.; Zhang, Z.; Xiao, Y.; Wei Wright, S. C.; Larrick, J. W. Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 16, 6552-6559, 2008.

17、 Kang, Y. M.; Xu, L. P.; Wang, B.; Chen, A. S.; Zheng, G. X. Immunosuppressant as adjuvant for tolerogenic immunization. J Immunol. 180, 5172-5176, 2008.

18、 Sun, Y.; Jiang, J.; Zhang, Z.; Yu, P.; Wang, L.; Xu, C.; Liu, W.; Wang, Y. Antioxidative and thrombolytic TMP nitrone for treatment of ischemic stroke. Bioorg. Med. Chem. 2008. in press

19、 Chen, W-M.; Cheng, C.; Li, B-Z.; Ho, T-L.; Cai, Z-S.; Wang, Y.; Sun, P-H. 4-Mercaptopyridine and aAmphoteric analogs: novel protection of aryl bromides in strong alkali.Helvetica Chimica Acta. 2008, in press

20、蒋杰, 李明, 向继洲. 知母宁抗流感病毒作用研究. 中国药师, 7, 335-338, 2004.

21、蒋杰, 向继洲. 知母宁体外抗单纯疱疹病毒I型活性研究. 中国药师, 7, 666-670,2004.

22、索绪斌, 邓英杰, 井水泉, 杜松, 李春蕾, 钟海军, 郝爱军. HPLC-ELSD大孔吸附树脂分离法测定黄芪皂苷脂质体的包封率.中国药学杂志, 9, 680-682, 2004.

23、张在军，向军俭，黄峙. 过敏症免疫治疗的新策略. 中国免疫学杂志, 20, 635-638,2004.

24、杨兆琪, 邱国福, 梁淑彩, 胡先明. 肿瘤血管生成抑制剂CA-4的合成. 中国现代应用药学, 22, 210-211, 2005.

25、张在军，毛露甜，向军俭等. Dot-ELISA法同时检测多种食品过敏原的实验研究. 食品科技, 4, 79-81, 2005.

26、向军俭, 张在军, 毛露甜等. 食品过敏原体外激发小鼠致敏肥大细胞组胺释放. 广东医学, 26, 4-6, 2005.

27、张在军, 向军俭. 河虾中主要过敏原鉴定及分离纯化. 广东医学, 27, 650-651,2006.

28、张在军, 王玉强. NF-κB 与癌症发生的关系研究进展. 广东医学, 27, 180-182,2006.

29、索绪斌, 邓英杰, 郝爱军, 张晓燕. 月桂酰吲达帕胺的电离常数及分配系数的测定.沈阳药科大学学报. 22, 335-337, 2005.

30、杨兆琪. 抗癌药Combretastatin-4结构修饰的研究进展. 化学通报, 69, 80, 2006.

31、杨兆琪, 苏江涛. β-偕二甲基环丙烷氨基酸酯的合成. 化学试剂, 28, 375-376,2006

32、贺焕华、于沛、黄克难 “气相色谱法测定头孢吡肟中N-甲基吡咯烷杂质含量” 中国抗生素杂志, 32, 87, 2007.

33、于沛、黄必勇 “头孢他啶中间体7-氨基-3-(1-吡啶甲基)头孢烷酸两种制备工艺方法及其特点分析”中国医药工业杂志, 332, 2007

34、索绪斌, 邓英杰, 张涵, 杨兆琪, 张在军, 王玉强. 月桂酰吲达帕胺脂质体中药物含量及包封率的测定. 中国新药杂志, 16, 230-233, 2007.

35、索绪斌, 张云凌, 杨兆琪, 张在军, 王玉强. 穿心莲内酯固体分散体的制备及体外溶出度测定. 中成药. 29, 594-596, 2007.

36、索绪斌, 邓英杰, 张涵, 杨兆琪, 王玉强. 吲达帕胺前体药物脂质体的制备. 中国医院药学杂志., 27, 431-434, 2007.

37、索绪斌, 邓英杰, 张涵, 王玉强. 月桂酰吲达帕胺脂质体的制备及质量控制. 中国新药杂志., 18, 69-71. 2007.

38、李康, 杨兆琪, 文富华, 孙平华. 罗匹尼罗中间体2-甲基-3-硝基苯乙酸的合成. 中国药房, 18, 1467-1468, 2007.

39、孙平华, 杨兆琪. 高效液相色谱法测定板蓝根注射液中鸟苷和尿苷的含量. 中华中医药学刊, 25, 1728-1729, 2007.

新药所骨干人员申请和已授权的代表性发明专利:

1. Farquhar, D., Wang, Y. Novel antitumor aldophosphamide analogues, US 5,091,552, February 1992.

2. Farquhar, D., Wang, Y. Novel antitumor aldophosphamide glycoside and dideoxyuridine derivatives, US 5,187,266, 1993.

3. Lown, J. W., Wang, Y., Wei, L. Cyclopropylpyrroloindole-Oligopeptide Anticancer Agents, US 5,502,068, March 1996.

4. Wang, Y., Wright, S. C., Larrick, J. W. DNA-binding indole derivatives, their prodrugs and immunoconjugates, US 5,843,937, 1998.

5. Wang, Y., Ye, W., Larrick, J. W, Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 6,444,702, 2002.

6. Wang, Y., Ye, W., Larrick, J. W, Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 6,620,845, 2003.

7. Wang, Y., Larrick, J. W. Antioxidant nitroxides and nitrones as therapeutic agents. US 6,717,012, April 2004.

8. Wang, Y. Novel anticancer conjugates of camptothecin and unsaturated fatty acids. US 6,759416, 2004.

9. Wang, Y., Larrick, J. W. Antioxidant nitroxides and nitrones as therapeutic agents. US 6,852,889, 2005.

10. Wang, Y. Novel tumor-selective chemotherapeutic agents. US 20050250835 (pending, published on November 10, 2005).

11. Wang, Y., Ye, W., Larrick, J. W., Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 20060106222 (pending, published on May 18, 2006).

12. Wang, Y., Larrick, J. W., Wright, S. C. Compounds useful in coating stents to prevent and treat stenosis and restenosis, US 20070037739 (pending, published on February 15, 2007).

13. 王玉强等 “穿心莲内酯衍生物及其在制药中的应用” 发明专利申请号200710029644.3.

14. 于沛等 “头孢硫脒复盐及其制造方法”发明专利号 ZL 200410050902.2, 已授权.

15. 于沛等 “头孢匹胺钠的制备方法” 发明专利号200410027956.7, 已授权.

16. 于沛等 “一种稳定的头孢硫脒药物组合物” 发明专利申请号200410102451.2.

17. 于沛等 “一种头孢烯类鎓盐化合物及其制备方法和用它制备头孢吡肟的应用” 发明专利申请号200410015230.1.

18. 于沛等 “一种青霉素衍生物的结晶体及其制造方法” 发明专利申请号200710026940.8.

19. 于沛等 “一种呋脲苄青霉素晶体及其制备方法” 发明专利申请号200710026939.5.

20. 于沛等 “7-氨基-3-羟基甲基-3-头孢菌素-4-羧酸晶体及其制造方法” 发明专利申请号200710027208.2.

21. 索绪斌等 “包封两亲性药物的脂质体的制备方法及其制剂” 公开号：CN 1593387A.

22. 索绪斌等 “磺胺类化合物脂质体的制备及其制剂” 公开号：CN 1593430A