GS143 is a selective IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 suppressesNF-κB activation and transcription of target genes and does not inhibitproteasome activity. GS143 has anti-asthma effect .
Nuclear factor-kappa B (NF-κB) is known to regulate the expression of divergent genes involved not only in immune and inflammatory responses but also in cell death and survival. IκBα is the protein inhibitor of NF-κB whose phosphorylation is catalyzed by an IκB kinase (abbreviated IKK). GS143 is a selec¬tive IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 suppressed the transcription of TNFα-induced NF-κB with a mean IC50 value of 10.5 μM. GS143 also inhibited TNFα-induced expression of ICAM-1 in HT-29 colon cancer cells with an IC50 value of 6.1 μM. The production levels of TNFα and IL-1β in LPS-activated THP-1 cells were inhibited by GS143 with IC50 values of 5.3 μM and 2.1 μM, respectively[2]. In BALB/c mice, intranasal administration of GS143 (16-32 μg/kg) treatment suppressed antigen-induced NF-κB activation in the lung of sensitized mice. GS143 treatment also inhibited antigen-induced eosinophil and lymphocyte recruitment into the airways and the expression of Th2 cytokines and eotaxin in the airways[1].
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