Overview
- Favata, M.F. et al. (1998) J. Biol. Chem. 273, 18623.
- Duncia, J.V. et al. (1998) Bioorg. Med. Chem. Lett. 8, 2839.
Protect from light.
Alomone Labs U0126 inhibits P42/44 MAPK phosphorylation via MEK1/MEK2 in C6 glioma cells.Cells were grown to 70% confluence and serum starved for 1.5 h. The cells were then incubated for 2 h with various concentrations of U0126 (#U-400) and stimulated with 7 ng/ml PDGF-AA. Cell proteins were resolved by SDS-PAGE and probed with anti-phospho-P42/44 MAPK (upper panel) and with anti-P42/44 MAPK (lower panel). The phosphorylation of P42/44 decreased in a dose-dependent manner.
U0126 is a chemically synthesized organic compound that was initially recognized as a cellular AP-1 antagonist, and found to be a very selective and highly potent inhibitor of the Mitogen-Activated Protein Kinase (MAPK) cascade by inhibiting its immediate upstream activators, Mitogen-Activated Protein Kinase Kinase 1 and 2 (also known as MEK1 and MEK2, IC50: 70 and 60 nM respectively). U0126 inhibits both active and inactive MEK1,2, unlike PD098059 which only inhibits activation of inactive MEK1,2. Blockade of MEK activation would prevent downstream phosphorylation of a number of factors including p62TCF (Elk-1), an upstream inducer of c-Fos and c-Jun, components of the AP-1 complex.1-4
Inhibition of the MEK/ERK pathway by U0126 also prevents all effects of oncogenic H-Ras and K-Ras, inhibits part of the effects triggered by growth factors and blocks the production of inflammatory cytokines and matrix metalloproteinases.5-11
