p38 MAP Kinase Inhibitor X; BIRB 796

General description

A cell-permeable pyrazolo-napthalenyl urea compound that acts as a highly potent, slowly binding (IC₅₀ = 8 and 97 nM, respectively, against human p38α, respectively, with or without 2 h preincubation), but high affinity (t_1/2 of dissociation from human p38α = 23 h), p38-selective inhibitor by simultaneously targeting the ATP-binding site and an adjacent DFG-out conformation-specific allosteric cavity. It inhibits JNK2α2 and c-Raf-1 only at much higher concentrations (IC₅₀ = 98 nM and 1.4 µM, respectively) and displays little or no activity toward 10 other kinases (IC₅₀ >20 µM). Shown to inhibit LPS-induced TNF-α production in cultures in vitro (IC₅₀ = 18 and 780 nM using THP-1 cells and in human whole blood, respectively) and in mice in vivo (by 84% and 63%, respectively, with oral dosage of 30 mg/kg and 10 mg/kg).

A cell-permeable pyrazolo-napthalenyl urea compound that acts as a highly potent, slowly binding (IC₅₀ = 8 and 97 nM, respectively, against human p38α, respectively, with or without 2 h preincubation), but high affinity (t_1/2 of dissociation from human p38α = 23 h), p38-selective inhibitor by simultaneously targeting the ATP-binding site and an adjacent DFG-out conformation-specific allosteric cavity. It inhibits JNK2α2 and c-Raf-1 only at much higher concentrations (IC₅₀ = 98 nM and 1.4 µM, respectively) and displays little or no activity toward 10 other kinases (IC₅₀ >20 µM). Shown to inhibit LPS-induced TNF-α production both in vitro (IC₅₀ = 18 and 780 nM using THP-1 cells and in human whole blood, respectively) and in mice in vivo (by 84%; 30 mg/kg p.o.).

Legal Information

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

Other Notes

Liu. Y. and Gray, N.S., 2006. Nat. Chem. Biol.2, 358.Regan, J., et al. 2003. J. Med. Chem.46, 4676.Pargellis, C., et al. 2002. Nat. Struct. Biol.9, 268.Regan, J., et al. 2002. J. Med. Chem.45, 2994.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Regulatory Review (Z)