2007
Simple, mammalian cell-based assay for identification of inhibitors of the ErkMAP kinase pathway.
KREJČÍ, Pavel, Kateřina PEJCHALOVÁ a William R. WILCOXZákladní údaje
Originální název
Simple, mammalian cell-based assay for identification of inhibitors of the ErkMAP kinase pathway.
Autoři
KREJČÍ, Pavel (203 Česká republika, garant, domácí), Kateřina PEJCHALOVÁ (203 Česká republika, domácí) a William R. WILCOX (840 Spojené státy)
Vydání
Investigational New Drugs, 2007, 0167-6997
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 2.806
Kód RIV
RIV/00216224:14310/07:00067364
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000247275600013
Klíčová slova anglicky
Erk; inhibitor; FGFR3; growth arrest; screening; library
Změněno: 29. 4. 2014 09:37, prof. Ing. Petr Dvořák, CSc.
Anotace
V originále
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.
Návaznosti
MSM0021622430, záměr |
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