GS-143 is an inhibitor of IκBα ubiquitylation.[1] It inhibits ubiquitylation of phosphorylated IκBα mediated by the SCFβTrCP1 E3 ubiquitin ligase complex in vitro (IC50 = 5.2 μM) and reduces TNF-α-induced degradation of phosphorylated IκBα, but not β-catenin, another SCFβTrCP1 substrate, in HeLa S3 cells. GS-143 inhibits LPS-induced expression of TNF-α, IL-6, IL-12, ICAM-1, and NF-κB in THP-1 cells in a concentration-dependent manner. Intranasal administration of GS-143 (32 μg/animal) reduces the number of eosinophils, lymphocytes, and total cells in bronchoalveolar lavage fluid (BALF) in an ovalbumin-sensitized mouse model of allergic asthma.[2]
Reference:
[1]. Nakajima, H., Fujiwara, H., Furuichi, Y., et al. A novel small-molecule inhibitor of NF-κB signaling. Biochem. Biophys. Res. Commun. 368(4), 1007-1013 (2008).
[2]. Hirose, K., Wakashin, H., Oki, M., et al. GS143, an IκB ubiquitination inhibitor, inhibits allergic airway inflammation in mice. Biochem. Biophys. Res. Commun. 374(3), 507-511 (2008).