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@article{971626,
author = {Krejčí, Pavel and Pejchalová, Kateřina and Wilcox, William R.},
article_number = {4},
doi = {http://dx.doi.org/10.1007/s10637-007-9054-7},
keywords = {Erk; inhibitor; FGFR3; growth arrest; screening; library},
language = {eng},
issn = {0167-6997},
journal = {Investigational New Drugs},
title = {Simple, mammalian cell-based assay for identification of inhibitors of the ErkMAP kinase pathway.},
volume = {25},
year = {2007}
}
TY - JOUR
ID - 971626
AU - Krejčí, Pavel - Pejchalová, Kateřina - Wilcox, William R.
PY - 2007
TI - Simple, mammalian cell-based assay for identification of inhibitors of the ErkMAP kinase pathway.
JF - Investigational New Drugs
VL - 25
IS - 4
SP - 391-395
EP - 391-395
SN - 01676997
KW - Erk
KW - inhibitor
KW - FGFR3
KW - growth arrest
KW - screening
KW - library
N2 - The Erk MAP kinase pathway contributes to tumor development and thus represents an important therapeutic target. Several inhibitors of the Erk pathway are presently being evaluated in clinical trials for cancer, but show limited efficiency thus warranting discovery of more potent inhibitors. We have developed a novel mammalian cell-based assay that should facilitate the identification of such compounds by screening molecular libraries. In rat chondrosarcoma (RCS) cells, treatment with fibroblast growth factor 2 (FGF2) leads to sustained activation of the Erk pathway, resulting in growth arrest with more than an 80% cell count difference between control and FGF2-treated cells after 72 h of treatment. The extent of both Erk activation and the growth arrest can be precisely modulated by the FGF2 dose. We also demonstrate that FGF2-mediated activation of the Erk pathway is robust and has only a limited sensitivity to the available MEK inhibitors. The assay is rapid, sensitive and easily adapted to high throughput screening. A major advantage of this system is exclusion of toxic compounds as false-positive hits, given the nature of the RCS response to inhibition of the Erk pathway, i.e. growth.
ER -
KREJČÍ, Pavel, Kateřina PEJCHALOVÁ and William R. WILCOX. Simple, mammalian cell-based assay for identification of inhibitors of the ErkMAP kinase pathway. \textit{Investigational New Drugs}. 2007, vol.~25, No~4, p.~391-395. ISSN~0167-6997. Available from: https://dx.doi.org/10.1007/s10637-007-9054-7.
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