IQ-1S (free acid)

IQ-1S free acid is a prospective inhibitor of NF-κB/activating protein 1 (AP-1) activity with an IC₅₀ of 2.3±0.41 μM. IQ-1S free acid has binding affinity (K_d values) in the nanomolar range for all three JNKs with K_ds of 100 nM, 240 nM, and 360 nM for JNK3, JNK1, and JNK2, respectively. IC50 & Target: IC50: 2.3±0.41 μM (NF-κB/AP-1)^[1]
Kd: 100 nM (JNK3), 240 nM (JNK1), 360 nM (JNK2), 0.38 μM (CK1δ), 0.47 μM (PI3Kγ), 0.92 μM (MKNK2)^[1] In Vitro: Compound IQ-1S is a potent, noncytotoxic inhibitor of pro-inflammatory cytokine [interleukin (IL)-1α, IL-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon-γ, and granulocyte-macrophage colony-stimulating factor] and nitric oxide production by human and murine monocyte/macrophages. The effect of IQ-1S is evaluated on LPS-induced cytokine production in human PBMCs. Among the 12 cytokines analyzed, LPS (200 ng/mL) consistently induces five (IL-1α, IL-1β, IL-6, IL-10, and TNF-α) in PBMCs compared with DMSO-treated control cells. Production of all of these cytokines is significantly inhibited by 20 μM IQ-1S. Among them, TNF-α production is inhibited completely by IQ-1 (>99%), the levels of IL-1α, IL-1β, and IL-10 are decreased by 85%, and IL-6 production is decreased by 33%^[1]. In Vivo: When mice are dosed with 12.5 and 30 mg/kg IQ-1S (The sodium salt of IQ-1S) i.p., the serum exposure of the compound is also good, with AUC_0-12h values of 2.9 and 7.4 μM/h, respectively^[1].