Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134)
文献类型：期刊论文
| 作者 | Ning, M.; Zhou, C.; Weng, J.; Zhang, S.; Chen, D.; Yang, C.; Wang, H.; Ren, J. ; Zhou, L.; Jin, C.
|
| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2007-01 |
| 卷号 | 150期号:1页码:19-28 |
| 关键词 | nuclear receptor oestrogen mammary gland uterus |
| ISSN号 | 0007-1188 |
| DOI | 10.1038/sj.bjp.0706960 |
| 文献子类 | Article |
| 英文摘要 | Background and purpose: Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. Experimental approach: Competitive receptor binding and luciferase-based reporter methods were used to study the bioactivities of raloxifene analogues, followed by efficacy determination in breast cancer cell proliferation assay. ER antagonist effects were investigated in female rats by measuring uterine and mammary gland growth, using wet weight, BrdU incorporation and terminal end bud (TEB) as indicators. Key results: Five analogues, belonging to two different structural series and display higher binding affinities for ER alpha than ER beta were functionally evaluated. One such analogue, Y134, exhibited potent antagonist activity at ERs in CV-1 cells cotransfected with plasmids containing ER alpha or ER beta and oestrogen-response element-driven luciferase. The estimated IC50 value was 0.52 nM for ERa and 2.94 nM for ER, comparable to that of raloxifene. Little cytotoxicity was observed at Y134 concentrations below 10 mu M. Y134 suppressed oestrogen-stimulated proliferation of ER-positive human breast cancer MCF-7 and T47D cells. At an identical dose, administered to ovariectomized rats, Y134 was more effective than raloxifene at arresting oestrogen-induced outgrowth of TEB and mammary gland DNA synthesis, but their inhibitory effects on the uterus were comparable. Conclusions and Implications: Y134 is a potent ER antagonist with better mammary gland selectivity than raloxifene and shows potential for development as a new SERM for therapeutic use. |
| WOS关键词 | BREAST-CANCER ; REPLACEMENT THERAPY ; MAMMARY-GLAND ; ALPHA ; BETA ; COACTIVATORS ; ANTAGONISM ; ACTIVATION ; MECHANISM ; TAMOXIFEN |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000243528000004 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273365]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Wang, M-W |
| 作者单位 | 1.Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ning, M.,Zhou, C.,Weng, J.,et al. Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134)[J]. BRITISH JOURNAL OF PHARMACOLOGY,2007,150(1):19-28. |
| APA | Ning, M..,Zhou, C..,Weng, J..,Zhang, S..,Chen, D..,...&Wang, M-W.(2007).Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134).BRITISH JOURNAL OF PHARMACOLOGY,150(1),19-28. |
| MLA | Ning, M.,et al."Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134)".BRITISH JOURNAL OF PHARMACOLOGY 150.1(2007):19-28. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。