JNK Inhibitor XV, IQ-1S

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.).

Cell permeable: yes

Primary Target
JNK1,2,3

Reversible: yes

Secondary Target
PI 3-Kγ, CK1δ and MKNK2

Packaged under inert gas

Toxicity: Standard Handling (A)

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

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

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