c-Jun N-Terminal Kinase (JNK) Inhibitor

IQ-1 (1) is an inhibitor of LPS-induced NF-κB/AP-1 activation with IC₅₀ of 2.3±0.41 μM,¹⁾ and binds to the c-Jun N-terminal kinase (JNK) family with the affinities as shown in Table 1. According to molecular docking analysis, the amine moiety in the Asn152 side-chain of JNK3 forms hydrogen bonds with both nitrogen and oxygen atoms in the oxime moiety of 1. 1 also inhibits pro-inflammatory cytokines* and nitric oxide production by human and murine monocyte/macrophages. In addition, the compound allows for the Wnt/β-catenin-driven long-term expansion of mouse ESCs and prevents spontaneous differentiation.²⁾

 *In reference 1, the authors show that interleukin (IL)-1α, IL-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon-γ, and granulocyte-macrophage colony-stimulating factor are inhibited by 1.

References

• 1) Identification and Characterization of a Novel Class of c-Jun N-terminal Kinase Inhibitors
• • I. A. Schepetkin, L. N. Kirpotina, A. I. Khlebnikov, T. S. Hanks, I. Kochetkova, D. W. Pascual, M. A. Jutila, M. T. Quinn, Mol. Pharmacol. 2012, 81, 832.
• 2) Wnt/β-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency
• • T. Miyabayashi, J.-L. Teo, M. Yamamoto, M. McMillan, C. Nguyen, M. Kahn, Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 5668.

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