IKKΒ-IN-5 is an orally active and selective inhibitor of IKKβ, with an IC50 value of 7.5 nM. It directly suppresses IKKβ phosphorylation, thereby mitigating NF-κB-mediated inflammation and survival signaling while enhancing autophagy (autophagy) flux. IKKΒ-IN-5 demonstrates a sixfold selectivity for IKKβ over the homologous kinase IKKα. This compound exhibits potent antiproliferative effects through a dual mechanism of inducing G₂/M cell cycle arrest and activating autophagy (autophagy), even under in vitro inflammatory stimulus conditions. IKKΒ-IN-5 shows favorable pharmacokinetic properties in vivo and inhibits tumor growth. It is applicable in research related to colorectal cancer and other potentially inflammation-driven malignancies.

IKKβ:7.5 nM

IKKβ-IN-5 (compound LP46) exhibits potent antiproliferative activity in RKO and HCT116 cells at 0-2 μM over 48 hours, while displaying low toxicity in NCM460 cells. It inhibits the phosphorylation of IKKβ at 0.75-3.0 μM for 48 hours, affecting the protein expression of IKKβ and its downstream target IκBα in these cell lines. Additionally, at 0.75-3.0 μM over 7 days, IKKβ-IN-5 maintains a long-term antiproliferative effect in RKO and HCT116 cells. It counteracts inflammation-induced cell changes by dual mechanisms—inducing G2/M cell cycle arrest and activating autophagy—thereby blocking NF-κB pathway activation and reducing downstream inflammatory responses in RKO and HCT116 cells. When used at 3 μM for 48 hours, IKKβ-IN-5 can directly counteract IKKβ-mediated pro-inflammatory and anti-autophagic effects in colorectal cancer cells with IKKβ knockdown or overexpression.