国家一类抗肿瘤新药有机硒化合物乙烷硒啉的药效药理作用

国家一类抗肿瘤新药有机硒化合物乙烷硒啉的药效药理作用

傅佳凝, 王静瑜, 王立辉, 王磊, 唐菀晨, 蔡高雄, 刘密, 曾慧慧^*

北京大学医学部天然药物与仿生药物国家重点实验室; 药学院化学生物学系, 北京 100191

收稿日期:2009-12-17 修回日期:2010-03-15 出版日期:2010-05-15 发布日期:2010-05-15
通讯作者: 曾慧慧*

Drug efficacy and pharmacological action of an organoselenium compound ethaselen, a novel antitumor drug

Jia-Ning Fu, Jing-Yu Wang, Li-Hui Wang, Lei Wang, Wan-Chen Tang, Gao-Xiong Cai, Mi Liu, Hui-Hui Zeng^*

State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2009-12-17 Revised:2010-03-15 Online:2010-05-15 Published:2010-05-15
Contact: Hui-Hui Zeng*

摘要/Abstract

摘要： 乙烷硒啉是由北京大学药学院设计合成并具有国际国内自主知识产权的有机硒化合物, 其生物学靶点为硫氧还蛋白还原酶。作为国家一类抗肿瘤新药, 乙烷硒啉正在进行临床I期试验。本篇综述主要介绍目前已研究发表的乙烷硒啉的药效药理作用, 包括体内体外的抗肿瘤作用及免疫调节功能。这些结果为乙烷硒啉进行更深入的抗癌临床研究提供了理论基础及治疗思路。

关键词: 乙烷硒啉, 有机硒化合物, 抗肿瘤作用, 免疫调节, 硫氧还蛋白还原酶

Abstract: Ethaselen, an organoselenium compound designed and synthesized in the School of Pharmaceutical Sciences, Peking University, has been entitled to independent intellectual property rights both at home and abroad. As one of the novel antitumor drugs, ethaselen has been extensively studied in Phase I clinical trial, and its biological target is thioredoxin reductase. In this review, we focus on the ethaselen’s efficacy and pharmacological actions, including antitumor effects both in vitro and in vivo, and immunologic functions. These research findings not only provide the theoretical basis for the anticancer study of ethaselen, but also guide the clinical trial of ethaselen.

Key words: Ethaselen, Organoselenium compounds, Antitumor effect, Immunologic function, Thioredoxin reductase

中图分类号:

R962

Supporting:

Foundation item: National Natural Science Foundation of China (Grant No. 30472036).
^*Corresponding author. Tel.: 86-10-82802878;

傅佳凝, 王静瑜, 王立辉, 王磊, 唐菀晨, 蔡高雄, 刘密, 曾慧慧^*. 国家一类抗肿瘤新药有机硒化合物乙烷硒啉的药效药理作用[J]. .

Jia-Ning Fu, Jing-Yu Wang, Li-Hui Wang, Lei Wang, Wan-Chen Tang, Gao-Xiong Cai, Mi Liu, Hui-Hui Zeng^* . Drug efficacy and pharmacological action of an organoselenium compound ethaselen, a novel antitumor drug [J]. .

参考文献

[1] El-Bayoumy, K. J. Drugs Fut. 1997, 22, 539-545.
[2] Ip, C.; Lisk, D.J.; Ganther, H.; Thompson, H.J. Anticancer Res. 1997, 17, 3195-3199.
[3] Rao, C.V.; Wang, C.Q. Cancer Res. 2001, 61, 3647-3652.
[4] El-Bayoumy, K.; Narayanan, B.A.; Desai, D.H.; Narayanan, N.K.; Pittman, B.; Amin, S.G.; Schwartz, J.; Nixon, D.W. Carcinogenesis. 2003, 9, 1505-1514.
[5] Shi, C.; Yu, L.Z.; Yang, F.G.; Yan, J.; Zeng, H.H. Biochem. Biophys. Res. Commun. 2003, 309, 578-583.
[6] Zhao, F.; Yan, J.; Deng, S.; Lan, L.; He, F.; Kuang, B.; Zeng, H.H. Cancer Lett. 2006, 236, 46-53.
[7] Xing, F.; Li, S.; Ge, X.; Wang, C.; Zeng, H.H.; Li, D.; Dong, L. Oral Oncol. 2008, 44, 963-969.
[8] Peng, Z.F.; Lan, L.X.; Zhao, F.; Li, J.; Tan, Q.; Yin, H.W.; Zeng, H.H. J. Zhejiang Univ. Sci. B. 2008, 9, 16-21.
[9] Tan, Q.; Li, J.; Yin, H.W.; Wang, L.H.; Tang, W.C.; Zhao, F.; Liu, X.M.; Zeng, H.H. Invest. New Drugs. 2010, 28, 205-215.
[10] Lan, L.X.; Zhao, F.; Wang, Y.; Zeng, H.H. Eur. J. Pharmacol. 2007, 555, 83-92.
[11] Deng, S.J.; Kuang, B.; Zhou, X.; Yan, J.; Zhao, F.; Jia, X.Y.; Zeng, H.H. J. Peking Univ (Health Sci.). 2003, 35, 108-109.
[12] Li, J.; Fang, J.C.; Zeng, H.H. Chin. J. New Drugs Clin. Rem. 2008, 27, 839-843.
[13] Wang, Y.R.; Xiao, J.J.; Dong, X.M.; Meng, S.C.; Deng, S.J.; Kuang, B.; Yan, J.; Zhao, F.; Zeng, H.H. J. Peking Univ (Health Sci.). 2006, 38, 634-639.
[14] Wang, Y.R.; Zeng, H.H. J. Peking Univ (Health Sci.). 2005, 37, 421-424.
[15] Hu, S.K.; Yu, Y.; Zhang, R.J. J. Xi'an Jiaotong Univ (Med. Sci.). 2009, 30, 44-123.
[16] Shi, C.; Zeng, H.H.; Li, H.W. Chin. Med. J. 2003, 83, 1984-1988.
[17] Yan, J.; Deng, S.J.; Kuang, B.; Zeng, H.H. J. Chin. Pharm. Sci. 2004, 13, 199-204.
[18] Arnér, E.S.; Holmgren, A. Semin. Cancer Biol. 2006, 16, 420-426.
[19] Urig, S.; Becker, K. Semin. Cancer Biol. 2006, 16, 452-465.
[20] Orrenius, S. Toxicol. Lett. 2004, 149, 19-23.
[21] Shi, W.X.; Stan, T.; Kenned, Y.L. J. Biol. Chem. 2006, 281, 10715-10726.
[22] Nouri, A.; Bergbaum, A.; Lederer, E. Eur. J. Cancer. 1991, 27, 608-612.
[23] Fatima, R.D.; Jose, A.; Maristela, T. J. Immunol. Methods. 2000, 241, 121-129.
[24] Hussain, R.F.; Nouri, A.; Oliver, R. J. Immunol. Methods. 1993, 160, 89-96.
[25] Chu, Y.J.; Li, X. Guangdong Trace Elem. Sci. 1997, 4, 281-287.
[26] Mitsuhiro, M.; Takayuki, I.; Shigeo, H.; Tadao, U.; Nobuo, I. Leuk. Res. 2009, 33, 119-120.
[27] Ge, W.; Ma, X.T.; Li, X.; Wang, Y.F.; Li, C.H.; Meng, H.X.; Liu, X.F.; Yu, Z.; You, S.G.; Qiu, L.G. Leuk. Res. 2009, 33, 948-957.
[28] Abe, Y.; Muto, M.; Nieda, M.; Nakagawa, Y.; Andrew, N.; Kaneko, T.; Gotod, S.; Yokokawa, K.; Suzuki, K. Exp. Hematol. 2009, 37, 956-968.
[29] Hiroshi, I.; Yutaka, H.; Teppei, N. Vet. Immunol. Immunopathol. 2009, 132, 85-90.
[30] Copier, J.; Dalgleish, A.G.; Britten, C.M. Eur. J. Cancer. 2009, 45, 1424-1431.
[31] Vaios, K.; Sanaa, K.; Theodora, K. Cancer Lett. 2009, 282, 159-166.