Discovery and characterization of a novel inhibitor of CDC25B, LGH00045

doi:10.1111/j.1745-7254.2008.00841.x

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	Discovery and characterization of a novel inhibitor of CDC25B, LGH00045
	Feng, Xu 2; Wang, Li-na 1; Zhou, Yue-yang 1; Yu, Hai-ping 1; Shen, Qiang 1; Zang, Yi1 ; Zhou, Yu-bo1 ; Li, Jing-ya1 ; Zhang, Hai-xia 2; Li, Jia1
刊名	ACTA PHARMACOLOGICA SINICA
	2008-10
卷号	29 期号:10 页码:1268-1274
关键词	LGH00045 high-throughput screening cell division cycle 25B inhibitor cyclin-dependent kinase 1 cell circle
ISSN号	1671-4083
DOI	10.1111/j.1745-7254.2008.00841.x
文献子类	Article
英文摘要	Aim: Cell division cycle 25 (CDC25) phosphatases have recently been considered as potential targets for the development of new cancer therapeutic agents. We aimed to discover novel CDC25B inhibitors in the present study. Methods: A molecular level high-throughput screening (HTS) assay was set up to screen a set of 48000 pure compounds. Results: HTS, whose average Z' factor is 0.55, was finished and LGH00045, a mixed-type CDC25B inhibitor with a novel structure and relative selectivity for protein tyrosine phosphatases, was identified. Furthermore, LGH00045 impaired the proliferation of tumor cells and increased cyclin-dependent kinase 1 inhibitory tyrosine phosphorylation. In synchronized HeLa cells, LGH00045 delayed cell cycle progression at the G(2)-M transition. Conclusion: LGH00045, a novel CDC25B inhibitor identified through HTS, showed good inhibition on the proliferation of tumor cells and affected the cell cycle progression, which makes it a good hit for further structure modification.
资助项目	Hi-Tech Research and Development Program of China[2006AA02Z315]
WOS关键词	DUAL-SPECIFICITY PHOSPHATASE ; HUMAN-CELLS ; TRANSGENIC MICE ; CANCER ; EXPRESSION ; CYCLE ; TRANSITION ; PROGNOSIS ; MITOSIS ; GROWTH
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3370800
出版者	BLACKWELL PUBLISHING
WOS记录号	WOS:000259937500018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272785]
专题	国家新药筛选中心药物安全性评价中心
通讯作者	Li, Jia
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Peoples R China
推荐引用方式 GB/T 7714	Feng, Xu,Wang, Li-na,Zhou, Yue-yang,et al. Discovery and characterization of a novel inhibitor of CDC25B, LGH00045[J]. ACTA PHARMACOLOGICA SINICA,2008,29(10):1268-1274.
APA	Feng, Xu.,Wang, Li-na.,Zhou, Yue-yang.,Yu, Hai-ping.,Shen, Qiang.,...&Li, Jia.(2008).Discovery and characterization of a novel inhibitor of CDC25B, LGH00045.ACTA PHARMACOLOGICA SINICA,29(10),1268-1274.
MLA	Feng, Xu,et al."Discovery and characterization of a novel inhibitor of CDC25B, LGH00045".ACTA PHARMACOLOGICA SINICA 29.10(2008):1268-1274.