General description

A cell-permeable, blood-brain barrier permeant, and orally active hydroxamate compound that is reported to inhibit MEK activity (IC₅₀ = 10-100 nM) without competing against ATP or Erk binding and exhibit excellent selectivity over 27 other cellular kinases, including JNK, MAPK2/ERK2, SAPK2a, SAPK2b, SAPK3, and SAPK4 (IC₅₀ >10 µM). Shown to be superior to PD 98059 (Cat. Nos. 513000 and 513001 and U0126 (Cat. No. 662005) in suppressing Erk1/2 phosphorylation in Hep3B, HepG2, PLC, and SKHep human liver cancer cells (IC₅₀﹤0.1 µM) in vitro and effectively reduce Erk1/2 phosphorylation in hippocampal tissue in mice (ED₅₀﹤50 mg/kg, i.p.) in vivo. Both PD184161 and U0126 are shown to induce necrosis of several types of glucose-deprived cells via an indirect action on the F0 component of the mitochondrial F1F0-ATPase/synthase.

A cell-permeable, blood-brain barrier permeant, and orally active hydroxamate compound that is reported to inhibit MEK activity (IC₅₀ = 10-100 nM) without competing against ATP or Erk binding and exhibit excellent selectivity over 27 other cellular kinases, including JNK, MAPK2/ERK2, SAPK2a, SAPK2b, SAPK3, and SAPK4 (IC₅₀ >10 M). Shown to be superior to PD 98059 and U0126 in suppressing Erk1/2 phosphorylation in Hep3B, HepG2, PLC, and SKHep human liver cancer cells (IC₅₀﹤0.1 M) in vitro and effectively reduce Erk1/2 phosphorylation in hippocampal tissue in mice (ED₅₀﹤50 mg/kg, i.p.) in vivo. Both PD184161 and U0126 are shown to induce necrosis of several types of glucose-deprived cells via an indirect action on the F0 component of the mitochondrial F1F0-ATPase/synthase.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Yip-Schneider, M.T., et al. 2009. J. Pharmacol. Exp. Ther.329, 1063.Duman, C.H., et al. 2007. Biol. Psychiatry61, 661.Klein, P.J., et al. 2006. Neoplasia8, 1.Thottassery, J.V., et al. 2004. Cancer Res.64, 4637.Yung, H.W., et al. 2004. Biochem. Pharmacol.68, 351.

Packaging

Packaged under inert gas

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Standard Handling (A)