Open AccessDiscovery and characterization of a novel inhibitor of CDC25B, LGH00045 1
Author(s) -
FENG Xu,
WANG Lina,
ZHOU Yueyang,
YU Haiping,
SHEN Qiang,
ZANG Yi,
ZHOU Yubo,
LI Jingya,
ZHANG Haixia,
LI Jia
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00841.x
Subject(s) - cdc25 , hela , cell cycle , kinase , protein tyrosine phosphatase , cell growth , phosphorylation , biology , chemistry , cancer research , microbiology and biotechnology , biochemistry , cell , cyclin dependent kinase 1
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.