Biochem/physiol Actions

Secondary TargetPI 3-Kγ, CK1δ and MKNK2

Reversible: yes

Cell permeable: yes

Primary TargetJNK1,2,3

General description

A cell-permeable indenoquinoxalinone-oxime (IQ) compound that acts as a potent, non-toxic, reversible, ATP-competitive, high-affinity inhibitor of JNK (K_d = 390, 360 and 87 nM for JNK1, JNK2 and JNK3, respectively) with moderate selectivity over CK1δ, PI 3-Kγ, and MKNK2 (IC₅₀ = 1.4, 1.2, and 1.8 µM, respectively). Shown to reduce c-Jun-Ser⁶³ phosphorylation, and block the production of LPS-induced TNF-α (IC₅₀ = 250 nM) and IL-6 (IC₅₀ = 610 nM) in MonoMac-6 monocytic cells and in human hPBMCs, respectively. Also shown to inhibit NF-κB/AP-1 reporter activity (IC₅₀ = 1.8 µM) in human THP1-Blue monocytic cells and diminish nitric oxide production in murine J774-A.1 macrophages (IC₅₀ = 12.5 µM). Exhibits favorable pharmacokinetics properties and efficiently reduces ovalbumin-induced CD⁺ T-cell immune inflammation in a murine delayed-type hypersensitivity model (12.5 mg/kg, two per day dosage, i.p.).

Legal Information

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

Other Notes

Schepetkin, I.A., et al. 2012. Mol. Pharmacol.81, 832.

Packaging

25 mg in Glass bottle

Packaged under inert gas

Reconstitution

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

Warning

Toxicity: Standard Handling (A)