Discovery and biological characterization of a novel series of androgen receptor modulators

doi:10.1038/bjp.2008.107

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	Discovery and biological characterization of a novel series of androgen receptor modulators
	Zhou, C.1,2; Wu, G.1,2; Feng, Y.1,2; Li, Q.1,2; Su, H.1,2; Mais, D. E.1,2; Zhu, Y.1,2; Li, N.1,2; Deng, Y.3; Yang, D.3
刊名	BRITISH JOURNAL OF PHARMACOLOGY
	2008-05
卷号	154 期号:2 页码:440-450
关键词	nuclear receptor androgen prostate cancer
ISSN号	0007-1188
DOI	10.1038/bjp.2008.107
文献子类	Article
英文摘要	Background and purpose: Selective androgen receptor modulators are of great value in the treatment of prostate cancer. The purpose of this study was to provide a preliminary characterization of a new class of non-steroidal androgen receptor modulators discovered in a high-throughput screening campaign. Experimental approach: Competitive receptor binding, luciferase-based reporter methods, cell proliferation and in vivo assays were employed to evaluate an initial set of compounds from chemistry efforts. Key results: Forty-nine analogues from the chemistry efforts showed high affinity binding to androgen receptors, agonist and/or antagonist activities in both CV-1 and MDA-MB-453 transfection assays. A proliferation assay in LNCaP cells also exhibited this profile. A representative of these non-steroidal compounds (compound 21) was devoid of activity at other nuclear receptors (oestrogen, progesterone, glucocorticoid and mineralocorticoid receptors) in the CV-1 co-transfection assay. At the same time, in an immature castrated rat model, it behaved as an androgen receptor antagonist against the growth of prostate, seminal vesicles and levator ani induced by exogenous androgen. Separation of compound 21 into its enantiomers showed that nearly all the androgen receptor modulating activity and binding resided in the dextrorotatory compound (23) while the laevorotatory isomer (22) possessed weak or little effect depending on the cell type studied. Conclusions and implications: These non-steroidal compounds may represent a new class of androgen receptor modulators for the treatment of not only prostate cancer but other clinical conditions where androgens and androgen receptors are involved in the pathological processes.
WOS关键词	CLINICAL-SIGNIFICANCE ; BREAST-CANCER ; ANTIANDROGEN WITHDRAWAL ; ANTAGONISTS ; BICALUTAMIDE ; POTENT ; ALPHA ; TUMOR ; ASSAY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000255755900016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272924]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室分析化学研究室
通讯作者	Wang, M-W
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 2.Chinese Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 3.Sichuan Univ, Dept Med Chem, W China Sch Pharm, Chengdu 610064, Peoples R China
推荐引用方式 GB/T 7714	Zhou, C.,Wu, G.,Feng, Y.,et al. Discovery and biological characterization of a novel series of androgen receptor modulators[J]. BRITISH JOURNAL OF PHARMACOLOGY,2008,154(2):440-450.
APA	Zhou, C..,Wu, G..,Feng, Y..,Li, Q..,Su, H..,...&Wang, M-W.(2008).Discovery and biological characterization of a novel series of androgen receptor modulators.BRITISH JOURNAL OF PHARMACOLOGY,154(2),440-450.
MLA	Zhou, C.,et al."Discovery and biological characterization of a novel series of androgen receptor modulators".BRITISH JOURNAL OF PHARMACOLOGY 154.2(2008):440-450.