Podrobný výpis o publikaci

KREJČÍ, Pavel, Kateřina PEJCHALOVÁ a William R. WILCOX. Simple, mammalian cell-based assay for identification of inhibitors of the ErkMAP kinase pathway. Investigational New Drugs. 2007, roč. 25, č. 4, s. 391-395. ISSN 0167-6997. Dostupné z: https://dx.doi.org/10.1007/s10637-007-9054-7.

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Základní 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
Originální 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
Doi	http://dx.doi.org/10.1007/s10637-007-9054-7
UT WoS	000247275600013
Klíčová slova anglicky	Erk; inhibitor; FGFR3; growth arrest; screening; library
Štítky	rivok, ZR
Změnil	Změnil: prof. Ing. Petr Dvořák, CSc., učo 47260. Změněno: 29. 4. 2014 09:37.

Anotace
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.

Anotace

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	Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie
MSM0021622430, záměr	Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie