In vitro
As a novel mitogen-activated protein kinase/ERK kinase (MEK) inhibitor, PD184352 inhibit ERK1/2 pathway and ERK5 pathways. In serum-starved CCl39 ERK5 cells, PD184352 inhibited FBS-induced ERK1 activation with an IC50 of below 1 uM. PD184352 also inhibited FBS-induced cyclin D1 expression and cell-cycle re-entry without inhibiting ERK5. Serum-stimulated DNA synthesis and cyclin D1 expression was inhibited by low doses of PD184352, which abolished ERK1 activity but had no effect on ERK5. In cycling cells PD184352 caused a dose-dependent G1 arrest and inhibition of cyclin D1 expression at low doses, which inhibited ERK1 but were without effect on ERK5. In quiescent cells, serum-stimulated ERK1 activity was completely inhibited by PD184352 with an IC50 below 1 uM, whereas ERK5 activation was unaffected even at 20 microM.
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